A Closer Look at Color Blindness

Catherine on June 9, 2025

Close-up human eye representing color blindness and vision differences.

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

Have you ever met someone who can’t tell red from green or struggles to distinguish certain shades? This condition is called color blindness, and for many people, it’s something they’re born with. Color blindness doesn’t mean seeing the world in black and white. Most people with color blindness can still see colors, just not in the usual way. 

The most common type is red-green color blindness, where someone has trouble telling the difference between those two colors. Less common types include blue-yellow color blindness and total color blindness, which is very rare. These conditions affect how the light-sensitive cells in the eyes work. But what causes it and is it mostly  genetic?

You may want to read: Genetics of Color Blindness

What Is Color Blindness?

Color blindness happens when your eyes don’t detect colors properly. This is usually because some of your cone cells, special nerve cells, called photoreceptors,  in your eyes are missing or don’t work well. Cone cells detect light and color. You normally have three types that respond to red, green, and blue light. When one or more types of cones don’t function as they should, your ability to see certain colors or shades becomes limited. Most people with color blindness can still see colors, just differently than others. Only very rare cases involve seeing only shades of gray.

You may want to read: Visual Acuity: Seeing Clearly Through Science and Genetics

Studies on Secondary Color Blindness

Not all cases of color blindness are inherited. Some people develop it later in life due to aging, eye injuries, certain diseases like diabetes or glaucoma, or as a side effect of medications. These are acquired forms of color blindness.

One study looked into how type II diabetes can affect color vision. It included 343 participants and examined 673 eyes using a test called the Farnsworth-Munsell 100 Hue Test. The findings share that about 43% of people with type II diabetes showed some form of impaired color vision , and the rates were nearly the same whether or not the person had diabetic retinopathy. Most of the color vision problems involved difficulty telling apart blue and yellow shades. 

However, when researchers used a special analysis technique called the moment of inertia, they didn’t find any consistent patterns, such as red-green or blue-yellow defects. This suggests that color confusion in diabetic individuals may be more random and severe rather than following typical color blindness types.

The study identified several other factors that were linked to a higher chance of having color vision problems. One of the most significant was clinically significant macular edema , which tripled the risk. People with higher intraocular pressure , even if still within the normal range, were also more likely to experience color vision loss. Another unexpected factor was elevated heart rate, which showed a weaker but still meaningful connection. While there were slightly higher rates of impaired color vision among women and those with certain types of cataracts (like posterior subcapsular cataracts), these weren’t strong enough to remain significant when other variables were considered. Together, these findings highlight that color vision issues in diabetes aren’t just tied to obvious eye disease, like diabetic retinopathy.

 

Color vision changes might not seem like a big problem at first, but they can have a serious impact on daily tasks. People with impaired color vision  may struggle with recognizing traffic lights, reading charts that use color coding, or picking out ripe fruits. These issues can also affect job performance in professions where color recognition is important. 

 

The study suggests that individuals with diabetes, especially those with macular swelling or higher eye pressure might benefit from functional vision testing and counseling. Even though these color vision problems might go unnoticed in a regular eye exam, they represent a real and often overlooked challenge in living with diabetes.

Is There a Cure for Color Blindness?

While there’s no cure for genetic color blindness, there are ways to manage it and adapt:

  • Color identification tools – Apps and devices can help label or recognize colors more accurately.
  • Special glasses or lenses – Some people benefit from glasses designed to improve contrast and enhance color differences, especially for red-green color blindness. These don’t work for everyone, but they can help in certain situations.
  • Adaptation strategies – Many people simply learn to rely on labels, organization, or pattern cues rather than color alone.

References:




The Genetics of Dyslexia

Catherine on June 8, 2025

Child with dyslexia surrounded by jumbled letters representing reading difficulty.

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

For people with dyslexia, everyday reading tasks may feel like decoding a foreign language. It’s frustrating, especially when one’s effort doesn’t seem to match results. But the root cause isn’t a lack of will, it’s in how the brain interprets written language. Genetics is helping explain why some brains are simply built to learn and process information differently.

Affecting up to 10% of the population, dyslexia challenges traditional notions of learning because it’s not caused by a lack of effort or intelligence. Understanding these roots may help improve diagnosis and intervention.

What is Dyslexia? 

Dyslexia is a specific learning difficulty that primarily affects reading, spelling, and writing. Individuals with dyslexia often struggle with decoding words, recognizing written symbols, and processing phonological information or the sounds of language. These difficulties may appear despite normal intelligence and access to education.

While reading challenges are the most visible symptoms, dyslexia may also affect working memory, rapid naming, and processing speed. It’s a lifelong condition, but with the right strategies and support, people with dyslexia can thrive academically and professionally.

You may want to read: How Genetics Shape Spatial Attention: A Deep Dive into Cognitive Abilities

What Are The Symptoms of Dyslexia? 

Dyslexia affects people differently, but the following are some common symptoms:

  • Difficulty reading aloud or reading slowly: A person with dyslexia may read word by word, often struggling to sound out longer or unfamiliar words. This happens because their brain takes more time to connect letters with sounds.
  • Trouble spelling even simple words: Spelling can be inconsistent. A person might spell the same word differently in the same paragraph. This is due to difficulty remembering how words are built phonetically or visually.
  • Problems matching letters to sounds: This is called phonological processing. People with dyslexia may not recognize that the letter b makes the b sound. This makes it hard to sound out words when reading or spelling.
  • Confusing similar-looking letters These are called mirror letters and are often flipped. Some letters like  b and d, or p and q.  It’s not a vision problem, it’s a brain processing issue where the brain misinterprets orientation.
  • Difficulty remembering sequences (like the alphabet or days of the week): Some people with dyslexia have trouble recalling things in order. This affects learning the alphabet, spelling rules, and even instructions that follow steps.
  • Struggling with writing or organizing thoughts on paper
     Writing may appear messy or disorganized. A person might know what they want to say but struggle to put it in a clear order or find the right words to write down.
  • Trouble learning new languages
     Learning a second language relies on similar skills as reading: decoding, listening, and remembering sounds. For someone with dyslexia, this may feel especially overwhelming.

You may want to read: Is Math ability Determined by Genetics?

What Causes Dyslexia?

The causes of dyslexia are multifactorial, meaning they stem from both genetic and environmental influences. While educational settings and early childhood experiences may shape how dyslexia manifests, research confirms that inherited factors play a major role in its development.

The Genetics Behind Dyslexia

Genetic factors linked to dyslexia don’t just influence reading ability, they help shape how the brain develops in the first place. Research shows that the genes that are associated with dyslexia can affect areas in the brain that are important for recognizing sounds and connecting them to written words, especially on the brain’s left side.

Brain scans of people with dyslexia often show differences in specific regions involved in reading, such as the temporoparietal and occipitotemporal areas. These differences are tied to genes that guide how brain cells move and settle into place during development.

Genes such as DCDC2 and KIAA0319 help guide neurons to their proper places in the brain. When this process is disrupted, the brain’s reading circuits may not develop well. Imaging studies show that people with dyslexia often have weaker connections in key language brain pathways like the arcuate fasciculus. This may slow down how quickly the brain combines what it hears with what it sees, which is critical for reading smoothly.

While reading instruction and intervention programs may help boost reading skills, they don’t completely reverse these brain differences. This shows that genetic wiring has a long-lasting effect on how the brain processes language and reading, even when external support is provided.

T Twin studies provide some of the strongest evidence that dyslexia has a genetic component. Researchers often compare monozygotic (identical) twins, who share 100% of their genes, with dizygotic (fraternal) twins, who share about 50%. 

When one identical twin has dyslexia, the other is much more likely to have it too, more often than in fraternal twin pairs. This higher concordance rate among identical twins suggests that genes play a major role in the development of dyslexia. Heritability estimates from these studies range between 40% and 70%, meaning that genetics accounts for a significant portion of the risk. However, the fact that concordance is not 100% even in identical twins also shows that environmental factors, such as early language exposure, teaching quality, and home literacy, also influence whether and how dyslexia develops. Twin research has helped us understand that dyslexia is not caused by a single gene but a combination of genetic and environmental factors.

A recent genome-wide association study (GWAS) investigated the genetic basis of dyslexia by analyzing data from over 51,800 adults who reported being diagnosed with dyslexia and more than one million individuals without the condition. Participants answered a survey question asking whether they had ever been diagnosed with dyslexia, allowing researchers to compare genetic differences between those who answered “yes” and those who answered “no.” The sample included both men and women, with the average age being around 50 years.

The study identified 42 genetic regions strongly linked to dyslexia, all meeting strict standards for statistical significance. Another 64 regions showed potential links, suggesting they may also be involved but need further study. These results support the idea that dyslexia is a polygenic trait  influenced by a wide range of genes, not just a single one.

To see whether these genetic effects differed by age or sex, researchers analyzed subgroups. The results were remarkably consistent. Genetic similarity (max 1.0) was 0.91 between males and females, and 0.97 between younger and older adults. This means the genetic influence on dyslexia appears stable across age and sex, although  more of the younger adults reported having dyslexia. About 5.3% of people in their twenties said they were affected, compared to just 3.2% of those in their eighties. This may reflect increased awareness, improved screening, or changes in how dyslexia is diagnosed over time.

Can you Treat Dyslexia?

There is no known cure for dyslexia, but effective management strategies may improve outcomes:

  • Structured literacy programs that focus on phonics, decoding, and spelling are proven to help children and adults build reading skills.
  • Assistive technologies like text-to-speech software and audiobooks support reading and comprehension.
  • Individualized education plans ensure that students receive accommodations and tailored instruction.
  • Awareness and self-advocacy help individuals understand their learning style and seek the support they need.

References

 

Why Does GPX1 Gene Matter for Your Health?

Catherine on June 6, 2025

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

Your body constantly works to keep itself healthy, especially by protecting its cells from damage. One of the ways it does this is through powerful antioxidant systems. One of the important parts in this system is a gene called GPX1.

Understanding this allows you to support your body with smarter steps to protect your wellness and keep your body strong. Understanding your genes can help you make smarter health choices and give your body the things it needs to thrive.

You may want to read: How Genetics Shapes Your Body’s Use to Glutathione

What is GPX1?

The GPX1 gene is an important part of your body’s defense system. It codes for the enzyme glutathione peroxidase 1, which helps clean up harmful byproducts and keeps oxidative stress in check. Oxidative stress happens when your body can’t keep up with the buildup of damaging byproducts created during normal cell activity.

What Does the GPX1 Do?

Inside each cell, chemical reactions are constantly taking place. Some of these reactions produce byproducts like hydrogen peroxide and lipid peroxides. If these aren’t properly cleared out, they can harm cells and contribute to oxidative stress.

This is where the GPX1 enzyme comes in. It helps break down those harmful substances, turning them into forms the body can safely remove. In doing so, GPX1 helps protect cells and supports overall health.

To work effectively, GPX1 relies on glutathione, one of the body’s most important natural antioxidants. Glutathione acts as a partner to GPX1, helping it neutralize damaging molecules. What makes GPX1 especially powerful is that it contains a rare building block called selenocysteine, a special version of the amino acid cysteine that includes the mineral selenium. This unique feature boosts the enzyme’s ability to fight oxidative stress.

What Is the C599T Genetic Variant?

While most people have the standard version of the GPX1 gene, some have a small genetic change called C599T also known as Pro198Leu, or the SNP rs1050450. This change replaces the C allele to a T allele. This small change may affect how well the GPX1 enzyme works. Studies have found that people with the T allele  of this SNP may have:

  • Weaker antioxidant protection:
     The T allele may make the enzyme less effective. This means your body isn’t as good at removing harmful substances that build up during normal cell activity.
  • Higher levels of oxidative stress:
     When your body can’t clear out these harmful substances properly, they build up and cause stress on your cells. This is called oxidative stress and may lead to cell damage over time.
  • Increased risk for certain health problems:
     If oxidative stress continues, it may raise your risk for serious conditions like cancer and heart disease. That’s why it’s important to support your body’s antioxidant system if you carry this gene variant.

How Can GPX1 Affect Health?

A research study on the GPX1 gene looked at the rs1050450 C>T  (C599T) variant and how it might affect people with diabetes. This gene makes an important antioxidant enzyme called glutathione peroxidase-1 (GPX1), which helps protect the body from oxidative stress. But when someone carries the T allele of this SNP, the enzyme doesn’t work as well.

Researchers studied over 1,100 people with diabetes from two separate groups in the UK. They found that people who carried the T allele were more likely to develop peripheral neuropathy, a type of nerve damage that can cause tingling, pain, or numbness in the hands and feet. In both groups, the risk was significantly higher in T allele carriers, even after accounting for other risk factors.

The study also found that people with the T allele had higher levels of oxidized LDL, a marker of oxidative stress. This means their bodies had a harder time fighting off damaging molecules.

Another study investigated the link between the GPX1 gene variant rs1050450 and ovarian cancer risk among Turkish women. The research involved 90 women diagnosed with ovarian cancer and 90 healthy controls. Results showed that women with the CC genotype (two C alleles) of the GPX1 variant had a lower risk of ovarian cancer. In contrast, those with the TT genotype had about three times higher risk. The presence of the single T allele was also associated with increased cancer risk. This study suggests that the rs1050450 variant in the GPX1 gene may influence ovarian cancer susceptibility in Turkish women, with the CC genotype potentially offering some protection and the TT genotype linked to greater risk.

Both studies show these findings suggest that reduced GPX1 activity due to the T variant may weaken the body’s antioxidant defense, making individuals more vulnerable to diseases related to oxidative damage. More research is needed, but these findings highlight how this gene could play a role in long-term health.

Understanding this helps us recognize how small changes in our genes like the rs1050450 SNP in the GPX1 gene may affect our body’s ability to handle oxidative stress. 

What Can You Do If You Have the  C599T Variant?

Even if you carry the T allele of the GPX1 gene variant C599T (rs1050450), there are things you can do to support your antioxidant system. Some nutrients can help either by supporting GPX1 directly or by acting as antioxidants on their own. Let’s explore what might help:

  • Glutathione: Since GPX1 needs glutathione to do its job, having enough of it is essential. Glutathione supplements can help in two ways. They support the GPX1 enzyme so it works properly. Glutathione also fights oxidative stress on its own, even without GPX1.
  • Vitamin C: This is one of the most well-known antioxidants. It helps protect cells from free radical damage and can be especially helpful for people with lower GPX1 activity.
  • Vitamin E: A vitamin known to protect the body from lipid-based free radicals, which are harmful fats that damage cells. If your GPX1 isn’t working at full strength, vitamin E can help fill the gap.
  • Vitamin A: Like vitamin E, vitamin A is especially good at targeting lipid-derived oxidative stress. It can help protect your cells if GPX1 is less effective because of the T allele.

References:

PON1 and Your Body’s Detox System

Catherine on June 6, 2025

DNA strand highlighting the genetic basis of the PON1 enzyme in body detoxification.

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

Our bodies are constantly exposed to harmful substances in the environment, from pesticides to pollution. Fortunately, we have natural defense systems designed to protect us from these toxins. One of these defenders is a gene called PON1, which produces an enzyme that plays a key role in detoxifying specific chemicals.

An enzyme is a type of protein that speeds up chemical reactions in the body. Think of enzymes as tiny helpers that keep biological processes running efficiently. In the case of PON1, the enzyme helps break down toxic substances into safer forms that the body can eliminate. However, not everyone has the same versions or amounts of this enzyme. These differences may affect how well your body handles toxic exposures.

Understanding how the PON1 enzyme works and how much of it your body makes, may offer insight into your ability to detox harmful chemicals. Some people inherit a more efficient version of the PON1 gene, while others may produce a less active form. This helps explain why some individuals are more sensitive to environmental toxins. 

You may want to read: The Role of Genetic Variations in Mercury Detoxification

What is PON1?

PON1 gene codes  for Paraoxonase 1, is an enzyme made in the liver and found in the blood attached to the HDL molecule known as the “good” cholesterol. 

High-density lipoprotein (HDL) exhibits cardio- and neuro-protective properties, which are thought to be promoted by PON1. Reduced levels of PON1 activity, characterized biochemically by elevated levels of homocysteine (Hcy)-thiolactone, oxidized lipids, and proteins modified by these metabolites, are associated with pathological abnormalities affecting the cardiovascular system (atherothrombosis) and the central nervous system (cognitive impairment and Alzheimer’s disease).

In addition to its role in cardiovascular and nervous system diseases by protecting the body from damage caused by oxidized fats, PON1 has many other antioxidant and detoxifying properties and can use several different substrates via its different types of enzyme activities (lactonase, arylesterase, aryldialkylphosphatase/paraoxogenase).  PON1 helps break down harmful chemicals, particularly organophosphates or OPs, a group of compounds commonly found in pesticides and nerve agents. 

How PON1 Detoxifies Harmful Substances

PON1 works alongside another group of enzymes called cytochrome P450, and together they convert harmful compounds, especially organophosphates—into less toxic forms the body can remove. Some of the key environmental harmful substances PON1 helps neutralize include:

  • Paraoxon: A breakdown product of the pesticide parathion. It inhibits acetylcholinesterase, an enzyme essential for nerve function, leading to dangerous nerve overstimulation.
  • Chlorpyrifos oxon: A toxic metabolite of chlorpyrifos, a common insecticide, that also impairs nerve signaling.
  • Diazinon oxon: A harmful version of diazinon, another widely used pesticide. It disrupts normal nervous system function.
  • Sarin and soman: Highly toxic nerve agents used in chemical warfare. Both inhibit acetylcholinesterase, causing severe and often fatal effects.

PON1 is especially active in the liver and blood, which are the body’s primary detoxification centers. The enzyme’s ability to break down these substances plays a critical role in protecting the nervous system and reducing toxic buildup.

The Role of Genetics

A study from California examined how people’s genes affect their ability to handle certain pesticides and what that means for their health. Researchers focused on PON1, the gene that helps break down chemicals like chlorpyrifos and diazinon, both widely used in agriculture.

They found that people living near farms that were using these pesticides were more likely to develop Parkinson’s disease if they had a version of the PON1 gene version called PON1-55 MM (variant L55M, SNP rs854560 genotype TT). This version produces less enzyme, reducing the body’s ability to detox these chemicals. The risk was even higher for individuals under 60, suggesting that early-life exposure may play a bigger role. Interestingly, there was no strong link between this PON1 variantand another pesticide called parathion, possibly because the body metabolizes it using other enzymes or other PON1 enzyme activities not affected by this SNP. 

This study shows that not everyone is equally protected from toxins. People with a less effective version of the PON1 gene may accumulate more harmful chemicals over time, increasing the risk of developing diseases like Parkinson’s. 

It’s a reminder that our genes and environment interact. For some individuals, living near farms or working with pesticides could be much more dangerous due to differences in how their detox system functions.

In another study, researchers examined 27 individuals who could detoxify pesticide byproducts diazoxon, chlorpyrifos-oxon, and paraoxon well. These substances are normally broken down by the PON1 enzyme in the liver and blood. The study found wide variation in detox rates among individuals: Diazoxon: up to 5.7-fold difference, Chlorpyrifos-oxon: up to 16-fold difference, and Paraoxon: up to 56-fold difference. This means some people were significantly better at clearing these toxins, especially paraoxon, than others.

These differences could be at least partly be explained by the PON-1 genetics. People with the PON1-192RR genotype (SNP rs662 CC homozygotes of Q192R) were more effective at detoxifying paraoxon and had higher activity against chlorpyrifos-oxon, but this did not apply to diazoxon. 

Detoxification of diazoxon seemed more dependent on environmental or likely unidentified genetic factors. Another key finding was that paraoxon was the hardest to detoxify. The liver broke down diazoxon and chlorpyrifos-oxon 55 and 65 times faster, respectively, compared to paraoxon. This slower detox rate helps explain why parathion, the pesticide that turns into paraoxon in the body, poses a greater health risk. Overall, the study highlights the complex relationship between genetics, enzyme activity, and environmental factors in determining how effectively the body removes harmful substances.

How PON1 Affects Health? 

Among the many genetic differences found in the PON1 gene, two common PON-1 variants have gained particular attention for their potential impact on health: the previously mentioned L55M and Q192R. The L55M variant refers to a change in the amino acid at position 55 of the PON1 protein, which may influence how much of the enzyme is produced and circulates in the bloodstream. Meanwhile, the Q192R variant has a role inthe enzyme’s function, specifically how well it can break down harmful substances such as a natural substrate oxidized low-density lipoprotein (LDL) and certain pesticides. 

Since both of the  L55M and Q192R, as well as other PON1 variants affect how active the PON1 enzyme is, individuals with different combinations of these gene variants may have varying levels of protection against oxidative stress and related diseases.

You may want to read: The Science Behind High-Density Lipoprotein: Genetics and Exercise Insights

Studies also suggest that the different versions of the Q192R variant  differ in their activity in neutralizing various harmful compounds. Because of this, people with different versions may have varying levels of protection against oxidative stress and the development of certain diseases. For example, a study done in Singaporean Chinese adults found that smokers with certain PON1 variants, specifically the Q192R (rs662-T) were more likely to develop coronary heart disease or CHD whereas the risk was higher for non-smokers with the PON-1 SNP rs3735590 . Therefore the PON1 gene variants associated with disease risk varied depending on smoking status. This suggests that the effect of PON1 on heart health is influenced by both genetics and environmental factors like smoking.

 

These findings point to a complex interaction between genes, lifestyle, and disease risk, an area that researchers still strive to  understand.

References




Genetics of Sickle Cell Anemia

Catherine on May 15, 2025

Close-up microscopic image of blood platelets and red blood cells, illustrating the cellular components involved in sickle cell anemia.

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

Sickle cell anemia is a well-known inherited blood disorder. Around 300,000 babies are born with sickle cell disease each year worldwide. The majority of people with sickle cell disease live in sub-Saharan Africa, India, the Mediterranean region, and the Middle East. In the United States, about 100,000 individuals are affected by the condition. It is caused by a genetic mutation that changes the shape and behavior of red blood cells (RBCs), leading to a range of health problems. Understanding the genetics behind sickle cell anemia helps explain how the disease is passed down, why it varies in severity, and how genetic screening can be used to manage it.

What Causes Sickle Cell Anemia?

Sickle cell anemia is caused by a mutation in the HBB gene, which provides instructions for making a part of hemoglobin — the protein in red blood cells that carries oxygen. This mutation changes just one DNA base, replacing adenine (A) with thymine (T). As a result, a single amino acid in the hemoglobin protein changes from glutamic acid to valine at position 6 of the beta-globin chain. This altered form of hemoglobin is called hemoglobin S (HbS).

Also read: The Genetics of beta-Thalassemia

Importance of Hemoglobin

Hemoglobin is a vital protein found in RBCs, and its main job is to carry oxygen from the lungs to the rest of the body. Every cell needs oxygen to produce energy, and hemoglobin ensures that oxygen is delivered efficiently. Once it drops off oxygen, hemoglobin also helps carry carbon dioxide, a waste product, back to the lungs to be exhaled. 

Without enough healthy hemoglobin, the body’s tissues and organs don’t get the oxygen they need, leading to fatigue, weakness, and more serious problems. In short, hemoglobin keeps your cells alive and your body functioning properly.

Why the Shape of Red Blood Cells Matters

The shape of RBCs is important because it helps them do their job well. Normal RBCs are round and flexible with a flattened, disc-like shape. This shape gives them a large surface area to carry more oxygen and allows them to squeeze through tiny blood vessels without getting stuck or damaged.

 

In people with sickle cell anemia, hemoglobin S (HbS) sticks together when oxygen levels are low. This causes red blood cells to become stiff and take on a crescent or “sickle” shape. These misshapen cells can block blood flow, break apart easily (leading to anemia), and cause pain, organ damage, or stroke.

Inheritance Pattern: Autosomal Recessive

Sickle cell anemia follows an autosomal recessive inheritance pattern. This means a person must inherit two copies of the HbS gene mutation — one from each parent — to have the disease.

 

  • Sickle cell disease occurs when a person has two sickle cell genes (HbSS) (mutation in both HBB gene copies).
  • Sickle cell trait occurs when a person has one sickle cell gene and one normal gene (HbAS). These individuals usually don’t have symptoms or have very mild ones, but they can pass the mutation  to their children.

For two parents who both have sickle cell trait (one mutated copy), each child has:

  • A 25% chance of having sickle cell disease (HbSS),
  • A 50% chance of having sickle cell trait (HbAS),
  • A 25% chance of having normal hemoglobin (HbAA).

Genetic Variants and Disease Severity

Not all people with sickle cell disease have the same symptoms. Some differences are due to other genetic factors. For example:

 

  • People with HbSC disease (one HbS gene and one gene for hemoglobin C, another variant) usually have milder symptoms than those with HbSS.
  • People with sickle beta-thalassemia (one HbS gene and one beta-thalassemia gene) may have a range of symptoms depending on the severity of the beta-thalassemia mutation.
  • Variants in genes that affect fetal hemoglobin (HbF) levels, such as the BCL11A gene, can reduce disease severity. Higher HbF levels can help prevent red blood cells from sickling.

BCL11A Gene

The BCL11A gene plays a key role in sickle cell disease by controlling the type of hemoglobin the body produces. Normally, babies are born with HbF, which is later replaced by adult hemoglobin (HbA). In people with sickle cell disease, the adult hemoglobin includes a faulty version called HbS.

BCL11A acts as a repressor—it switches off the production of HbF after birth. Scientists have discovered that reducing or turning off BCL11A can reactivate HbF production, even in adults. Increasing HbF levels helps because fetal hemoglobin prevents sickling of red blood cells, reduces symptoms, and improves overall blood health.

For this reason, BCL11A is a major target in gene therapy approaches for treating sickle cell disease. By silencing or knocking down BCL11A, therapies can boost HbF production and help protect patients from the damaging effects of HbS.

In a 2020 pilot study six patients with sickle cell disease were monitored for at least six months after receiving BCH-BB694 gene therapy, which uses shmiR-based knockdown to reduce BCL11A expression. The therapy led to strong and stable increases in fetal hemoglobin (HbF), with 20.4% to 41.3% of total hemoglobin being HbF and 58.9% to 93.6% of red cells showing HbF expression. During follow-up, sickle cell symptoms were reduced or disappeared. The results support BCL11A inhibition as a promising strategy for increasing HbF and show that this gene therapy approach may offer a good balance between safety and effectiveness.

Diagnosis and Genetic Testing

Sickle cell anemia is usually diagnosed with a blood test, often done in newborn screening programs. The test checks for different types of hemoglobin, including HbS. If a child is found to have the disease or trait, follow-up genetic testing can confirm the diagnosis and help understand the type of sickle cell condition.

Carrier testing for sickle cell trait is also important for couples planning a family, especially if both partners are from high-risk populations. Genetic counseling can help them understand the risks and options.

Why Sickle Cell Trait Still Exists

The sickle cell gene mutation remains common in some regions because of a natural advantage it provides. People with sickle cell trait are more resistant to severe malaria, especially from Plasmodium falciparum. This survival benefit explains why the mutation has persisted in areas where malaria is or was widespread.

Conclusion

Sickle cell anemia is a classic example of how a single gene mutation can lead to a serious health condition when inherited in a specific way. Advances in genetics have deepened our understanding of the disease and opened doors to new treatments, such as gene therapy and precision medicine. With early diagnosis, ongoing care, and better genetic awareness, people with sickle cell disease can live longer, healthier lives.

Read about other genetic conditions:

 

References

  1. https://jamanetwork.com/journals/jama/article-abstract/2793821
  2. https://www.nejm.org/doi/full/10.1056/NEJMoa2029392
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC3545189/

Leveraging Genomics to Tailor Antidepressant Therapy

Catherine on May 14, 2025

Did you know that depression can be influenced by DNA? In this article, we will discuss how mental health, depression, and genetics are related and how understanding these relationships can help you take action on optimizing your well-being.

Importance of Mental Wellness: Breaking the Taboo

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

Depression or major depressive disorder (MDD) is a multifactorial psychiatric condition. Individuals with depression often find themselves in a persistently low mood, anhedonia (inability to feel pleasure), cognitive disturbances, and other symptoms that impair daily functioning. 

Read our popular deep-dive on the Genetics of Depression

According to epidemiological data a lifetime prevalence of depression is approaching 15-20 % worldwide. Primary cause arises from complex interactions of genetics, neurochemical imbalance, dysregulated stress-axis activity, and environmental stress factors. 

Brain research shows that depression is linked to fewer mood-related neurotransmitters, disrupted glutamate activity, a smaller hippocampus, and poor communication between brain areas that control emotion and thinking. Converging evidence also highlights inflammatory processes and neurotrophic deficits, particularly decreased brain-derived neurotrophic factor (BDNF) expression, as contributors to disease onset and progression.

Antidepressants help correct chemical imbalances in the brain that are linked to depression. Most work by increasing the levels of mood-related neurotransmitters such as serotonin, norepinephrine, or dopamine. By restoring these signals, the drugs can lift mood, improve sleep and appetite, and reduce anxiety. They usually take a few weeks to reach full effect and should be used under a doctor’s guidance.

Antidepressant prescribing still relies heavily on trial-and-error. Around one-third of patients achieve remission with the first drug they receive, while many experience delayed benefit or troublesome side-effects. Pharmacogenomics, the study of how genetic variation influences drug response, offers a path out of this uncertainty. Over the past decade, and especially since 2023, large-scale studies and guideline updates have clarified which genes are involved, how strongly they affect efficacy and tolerability, and when testing should guide routine care. 

Serotonin-reuptake inhibitors (SSRIs)

SSRIs are a common class of antidepressant medicines that raise the level of serotonin. Serotonin is a chemical that helps regulate mood, and SSRIs act by blocking its re-absorption (reuptake) into the brain’s nerve cells after it is released. With more serotonin remaining active in the synapse (the space between two nerve cells), communication between neurons improves, which over several weeks can lift mood, reduce anxiety, and ease other depressive symptoms. 

Drugs such as fluoxetine, sertraline, and escitalopram belong to this group and are generally favored because they are effective, easy to dose, and safer than older antidepressants. However, they can still cause side effects like nausea, headache, or sleep changes and should be taken under medical supervision.

Core Genes: CYP2D6 and CYP2C19

CYP2D6 and CYP2C19 are genes that encode specific liver-based cytochrome P450 enzymes critical for drug metabolism. Most SSRIs are metabolised by cytochrome P450 enzymes. 

Alleles that reduce or stop the activity of CYP2D6 or CYP2C19 slow the serotonin clearance, leading to higher plasma levels, whereas increased-function alleles accelerate clearance and can lead to sub-therapeutic exposure.

  • CYP2D6 (chromosome 22q13) produces the CYP2D6 mono-oxygenase, which oxidizes roughly 20–25 % of all prescribed drugs, including many antidepressants (e.g., paroxetine, venlafaxine). It is highly polymorphic: more than 150 star-allele gene variants have been catalogued that can stop, reduce, normalise, or increase enzyme activity, giving rise to poor, intermediate, normal, or ultra-rapid metaboliser phenotypes.
  • CYP2C19 (chromosome 10q24) encodes CYP2C19, an enzyme that metabolises selective serotonin-reuptake inhibitors (escitalopram, sertraline). Like CYP2D6, the gene is highly variable, with common loss-of-function alleles (*2, *3) and a gain-of-function allele (*17) that respectively slow or speed drug clearance.

Because these variants can markedly alter plasma drug levels, clinical pharmacogenomic guidelines (e.g., CPIC, DPWG) recommend genotype-guided dosing or drug selection for medications that are substantially cleared by either enzyme to improve efficacy and reduce adverse effects.

In April 2023 the Clinical Pharmacogenetics Implementation Consortium (CPIC) updated its guideline, expanding the genotypes covered and providing concrete dose or drug-switch recommendations for 18 antidepressants. For example, for the SSRI escitalopram, CPIC recommends a 50% dose reduction or an alternative agent in CYP2C19 poor metabolisers, and avoiding paroxetine in CYP2D6 poor metabolisers altogether.

Clinical impact is now supported by meta-analysis: patients whose treatment was guided by a multi-gene panel, including CYP2D6 and CYP2C19, were 41-78 % more likely to achieve remission than those treated as usual. Importantly, the benefit was confined to randomised controlled trials, underscoring the need for rigorous implementation rather than opportunistic testing.

Transporters, Receptors and Downstream signalling

Drug concentration at the synapse is only half the story; neuronal response is equally shaped by the receptor and transporter genes. 

SLC6A4 Gene

SLC6A4 (solute carrier family 6 member 4) is the gene that encodes the serotonin transporter (often abbreviated SERT or 5-HTT), a membrane protein responsible for pumping serotonin back into presynaptic neurons after it has been released into the synaptic cleft. SLC6A4 gene is highly polymorphic. The best-studied variant is the serotonin-transporter-linked polymorphic region 5-HTTLPR located at the gene’s promoter, which exists mainly as long (L) and short (S) alleles; the S allele reduces transcription, leading to fewer transporters and altered serotonin tone.

Variants in SLC6A4, notably the L and S promoter repeat alleles, influence transcription and thus transporter density. Some, but not all studies link the L allele to greater SSRI response, while the S allele heightens the risk of gastrointestinal side-effects. 

A 2020 review of 49 studies found that people with major depression who carry the L form of the 5-HTTLPR variant in the SLC6A4 gene respond better to SSRI antidepressants than those with two S copies, but this benefit was clear only in Caucasian patients and did not appear in Asian groups or in studies using mixed drug classes. 

CPIC now classifies the S/S genotype as “possible reduced benefit” but does not yet mandate a dose change.

Recent scientific updates 

A study published in May of this year (2025) of 302 European patients with depression or anxiety who failed previous SSRI treatment found that certain genetic combinations in the serotonin system were much more common than in the general population. Patients carrying at least one G allele of the HTR1A rs6295 variant together with the short/short (SS) form of the SLC6A4 promoter variant 5-HTTLPR had the highest over-representation among those with failed treatment—about 74 % above expectations—suggesting this pairing greatly increases the risk of SSRI non-response and associated disability. The findings indicate that genotyping both the serotonin transporter (SLC6A4) and its autoreceptor (HTR1A) could help predict treatment failure and guide more effective antidepressant choices.

HTR2A and Other Genes

Serotonin-2A receptor (HTR2A) polymorphisms, particularly rs7997012, and BDNF Val66Met (rs6265) have been repeatedly associated with differential remission rates, although effect sizes are modest. A 2024 genome-wide association study (GWAS) in an Indian cohort added weight by identifying HTR2A and other synaptic signalling loci among the top hits for inadequate treatment response.

 

Moreover, downstream stress-axis genes such as FKBP5, which regulates glucocorticoid receptor sensitivity, may explain why some patients develop early adverse reactions or emotional blunting. Evidence here is still emerging, and no prescribing guideline incorporates these variants yet.

Ancestry

Most pharmacogenomic evidence has historically been derived from European populations, but allele frequencies can diverge widely among others. 

 

For instance, the CYP2C19*17 ultra-rapid allele is common in Northern Europeans yet rare in East Asians, whereas CYP2C19 loss-of-function alleles *2 and *3 occur in up to 20 % of Han Chinese. The 2024 Indian GWAS illustrates how locally generated data can uncover novel loci and improve predictive accuracy for the millions of patients in South Asia.

Beyond efficacy: genetics of adverse effects and withdrawal

Genes that influence transporter affinity or membrane pumps such as ABCB1 (P-glycoprotein) modulate central nervous system exposure and have been linked to sedation and weight gain. Meanwhile, emerging evidence suggests genetic predisposition to a difficult withdrawal: a 2024 meta-analysis noted that 43 % of long-term users experience discontinuation symptoms, with risk rising in CYP2D6 poor metabolisers who accumulate active drugs. Personalised tapering schedules based on metabolic genotype may therefore reduce withdrawal burden.

Clinical implementation: where testing is recommended today

International guidelines converge on three practical principles:

 

  1. Test before first prescription when using drugs for which genotype-based dose recommendations are clear (e.g., tricyclics, paroxetine, escitalopram, sertraline).
  2. Consider testing after inadequate response or intolerable side-effects to guide the next choice.
  3. Interpret results in context—age, comorbidities, and drug interactions can mimic genetic slow metabolism.

 

Health-system pilot studies show that pre-emptive panels integrated into electronic medical records are cost-effective, reducinghospitalisations from adverse reactions within two years of deployment. Some private insurances in the United States and several European countries now reimburse panel testing when guideline criteria are met.

Limitations and future directions of genetic testing

  • Genetic effect sizes are moderate. Genetics sets the range of likely outcomes, but environment, adherence, and placebo effects still contribute heavily.
  • Rare variants remain underexplored. Whole-genome sequencing is starting to reveal private mutations in CYP genes that conventional panels miss.
  • Multi-omics approaches beckon. Transcriptomic and metabolomic signatures measured at baseline may complement static DNA data, capturing dynamic state factors such as inflammation.
  • Ethical considerations. Testing can stigmatise or raise privacy concerns; informed consent and clear communication are essential.

 

The next frontier is adaptive prescribing algorithms that combine individual genotypes, Polygenic Risk Scores (PRS) , real-time mood rating and wearable-derived sleep data to adjust treatment weeks earlier than what is possible in today’s practice.

Conclusion

Genetic insights are already refining antidepressant therapy, moving psychiatry toward the precision enjoyed in oncology and cardiology. Testing for CYP2D6 and CYP2C19 variants has immediate, guideline-backed utility, while accumulating evidence on transporter variants and advanced PRS models promise progressively finer tailoring. Widespread implementation will require equitable sequencing across ancestries, clinician education, and integration with clinical decision support. Yet the trajectory is clear: as our understanding of the genetic response to antidepressants deepens, the era of “fail first, switch later” is giving way to informed, patient-specific care—offering faster relief and fewer harms for millions living with depression.

Reference

  1. https://pmc.ncbi.nlm.nih.gov/articles/PMC5640125/
  2. https://cpicpgx.org/guidelines/cpic-guideline-for-ssri-and-snri-antidepressants/
  3. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1276410/
  4. https://www.sciencedirect.com/science/article/abs/pii/S0165032720305188
  5. https://www.nature.com/articles/s41397-025-00370-5
  6. https://www.medrxiv.org/content/10.1101/2024.11.25.24317869v1.full-text



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Is Depression Genetic or Environmental?

Millions of individuals throughout the world have experienced or are currently experiencing depression, a prevalent mental condition that can significantly influence an individual’s quality of life and significantly reduce their ability to become functioning members of society.

According to the American Psychiatric Association, depression or major depressive disorder is a common and serious medical illness that negatively affects how you feel, think, and act. This condition can negatively impact a person’s feelings and emotions towards everything and everyone in their lives. People diagnosed with depression may frequently feel sadness or a loss of interest in things and people they once enjoyed and cared about.

There are tell-tale signs of depression but some of the common symptoms are feeling sad or down, changes in appetite, changes in sleeping patterns, increased fatigue, difficulty concentrating, and even thoughts of self-harm. While depression can affect a person of any age, experts have come to wonder, is there a genetic component to depression? Is depression purely influenced by a person’s environment, including their past traumas and current predicaments?

Life DNA

The truth is depression can be amplified by external variables such as stressful life events and stress, but DNA also has an important role in the development of this condition.

Environmental factors may also greatly contribute to developing depression. Chronic stress, traumatic childhood experiences, and recent life events are a few examples of environmental stressors linked to depression. A few other environmental factors may include:

  • Stressful Life Events. Depression may be brought on or made worse by the loss of a loved one, divorce, job loss, financial difficulties, or other significant circumstances.
  • Social Isolation. Depression can be exacerbated by a lack of social interaction and a sense of isolation.
  • Chronic Illness or Pain. Dealing with ongoing physical health problems or chronic pain can exacerbate depression due to its effects on overall well-being and quality of life.
  • Unhealthy Diet. Diets heavy in processed foods and poor nutrition may have a negative impact on brain health and exacerbate depressed symptoms.
  • Disrupted Sleep Patterns. Poor sleep hygiene, insomnia, or irregular sleeping habits can all lead to sadness.
  • Media and Social Media Influence. Social media comparisons, unrealistic body images, and constant negative news exposure can all have a negative impact on one’s self-esteem and heighten depression symptoms.
  • Parenting and Family Dynamics. Depression may arise as a result of dysfunctional family dynamics, parental neglect, or early trauma.

It’s essential to understand how these elements can interact with one another and a person’s genetic makeup to affect how likely they are to experience depression.

You may also like: What is 23andMe Raw Data?

Digging Into The Science: The Genetics of Depression

Untangling the complex web of causes for depression as a mental wellness issue requires an understanding of the genetics of depression. Can people be more predisposed to depression due to their unique genetic makeup? Is genetics just part of the puzzle and if so, how big of a part is it? If genetics has the potential to answer the long-standing questions of experts about how and why depression is developed, it is worth knowing more about the role of genetics even in the common person. 

According to rigorous research, depression has a genetic component. People who have experienced depression in their families may be more likely to experience it themselves. Certain genetic differences may increase a person’s susceptibility to depression when they are subjected to particular environmental stressors or causes. Studies on twins and families have revealed that there is a hereditary component to depression. A person with close relatives, such as parents or siblings who have depression, may be more likely to experience depression than those who have no family history.

Scientists have identified specific genes that might be associated with an increased risk of this mental condition. However, no single gene has been found to be solely responsible for depression. It is also difficult to pinpoint a few specific genes with a significant effect on depression risk due to their polygenic character. There are likely several genes that together contribute to depression, each having an impact.

Moreover, genetics and environmental factors can interact and cause, trigger, or amplify depressive symptoms. People with a genetic predisposition may be more vulnerable to specific environmental triggers or aggravators of depression, such as traumatic experiences or long-term stress. In sum, depression results from the interaction of a person’s environment and genetic predisposition, and it is influenced by all of these elements at different stages of development.

Types of Depression

Depression manifests in a variety of ways, each carrying its own distinct weight and being a complex and diverse emotional experience. There are several types of depression, some of which have symptoms that overlap. This is why the correct assessments of mental health professionals are needed when diagnosing depression in any individual. 

  1. Major Depressive Disorder (MDD). The most popular in the group, MDD is the most common type of depression. Symptoms may include low mood, fatigue, diminished interest, and feelings of worthlessness. There are subtypes of MDD:
    • Seasonal Affective Disorder (SAD). The feelings of persons who struggle with SAD change with the seasons. This kind of depression, which usually manifests during the short winter days, causes tiredness, changes in appetite, and a melancholic shroud that dissipates as soon as the sun shines again.
    • Prenatal and Postpartum Depression. The joy of new life isn’t a universal experience. Prenatal depression is depression that happens during pregnancy. Postpartum depression is depression that develops within four weeks of delivering a baby. Postpartum depression affects some new mothers, casting a shadow over what should be a time of celebration, and adding layers of guilt and hopelessness to an already challenging phase. The risk of developing this type of depression is higher during pregnancy and in the first year after childbirth. 
    • Atypical Depression. This type of depression frequently goes unnoticed under the garb of exhaustion, excessive sleep, overeating, and rejection sensitivity. The paradox is that despite the underlying sadness, it is possible to have brief moments of enjoyment.
  2. Persistent Depressive Disorder (Dysthymia). Dysthymia is a milder but longer-lasting form of depression. Symptoms last at least 2 years and have similar symptoms as major depression, but less in severity.
  3. Bipolar Disorder.  A confusing mix of emotions, bipolar disorder alternates between periods of sadness and mania with periods of neutral mood. A bipolar individual’s journey is turbulent because of the manic peaks and depressive depths, with spikes in energy followed by plunges into depression.
  4. Premenstrual Dysphoric Disorder (PMDD). A heightened form of premenstrual syndrome, PMDD throws a tidal wave of emotions into the lives of some women each month. Severe irritability, anxiety, or depression are some of the symptoms. After your period begins, these symptoms usually go away within a few days, but they can occasionally be so bad that they seriously affect your daily life.
  5. Situational or Reactive Depression. This particular sort of depression is a typical response to outside conditions that are brought on by life events such as loss, trauma, or stress. Even though it is frequently transient, it can be extremely emotionally taxing.

Is Postpartum Depression Genetic?

A type of depressive disorder that can develop after childbirth is called postpartum depression (PPD), often referred to as postnatal depression. Mood swings, irritability, and feelings of sadness are common in new mothers shortly after giving birth and are commonly referred to as the “baby blues.” Postpartum depression is more severe and pervasive than the “baby blues,” and it can have a significant impact on a mother’s capacity to care for herself and her child. its prevalence is estimated to be between 10% and 15% among new mothers. 

PPD symptoms might include ongoing melancholy, exhaustion, changes in eating and sleep patterns, trouble concentrating, feelings of guilt or worthlessness, and in extreme situations, thoughts of hurting oneself or the unborn child. Early identification and treatment of PPD are essential since it can affect a mother’s ability to carry out everyday tasks and form bonds with her child.

The chance of having PPD may have a hereditary component, according to research studies. Women who have family members who have experienced postpartum depression may be more likely to develop depression themselves. Genetics, however, is not the only cause; hormonal changes, psychological factors, lack of social support, and other life stressors all significantly contribute to the development of PPD.

There is still a chance that you could develop postpartum depression even if no women in your family have ever experienced it. Environmental elements also have an impact. For instance, a difficult childbirth could result in postpartum depression. Recognize the danger indicators and risk factors so you can seek assistance as soon as feasible. Risk elements consist of:

  • Any previous experience with depression
  • Events that caused stress during pregnancy
  • Challenging breastfeeding
  • Undesired pregnancy
  • Infants born with health issues
  • Relationship issues with your partner
  • A weak system of support
  • Financial difficulty

Although having a genetic predisposition may raise the risk, PPD is not a given. Many women with a family history of depression may not experience PPD. Contrarily, some women without a family history of depression may get PPD. Complex interactions exist between environmental and genetic risk factors. 

While undoubtedly a challenging and often scary battle for mothers, having PPD does not equate to being a bad parent. Therapy, support groups, lifestyle modifications, and in certain situations, medication, are all possible treatment choices. Early intervention can help moms regain their emotional health and capacity to care for their children while also dramatically improving outcomes.

Is Depression Related to Bipolar Disorder?

Both depression and bipolar disorder are mental health conditions that are related to one another but also have crucial differences. While mood disruptions are present in both illnesses, there are differences in the types and patterns of these changes. Both conditions have similar symptoms such as:

  1. Mood Episodes. Mood episodes are a feature of both depression and bipolar disorder. Anhedonia or the loss of ability to feel pleasure, a persistently depressed mood, and a number of other symptoms are all characteristics of depression. The same symptoms that characterize depressive episodes in depression also occur in bipolar disorder.
  2. Impaired Functioning. Both disorders have the potential to drastically reduce a person’s capacity for everyday living, impacting their ability to work, form relationships, and generally enjoy their lives.
  3. Overlap in Symptoms. During depression episodes, both bipolar disorder and depression might share the same symptoms, such as exhaustion, trouble focusing, and changes in food or sleep.

The key differences between bipolar disorder and major depressive disorder (sometimes also referred to as unipolar disorder) may include the lengths of episodes, varying degrees of symptoms, and the manic episodes that are more commonly attributed to bipolar disorder.

  1. Manic or Hypomanic Episodes. The existence of manic or hypomanic episodes in bipolar disorder is one of the main distinctions. People who go through these periods report higher mood, greater energy, impulsivity, racing thoughts, and occasionally a reduced need for sleep. Hypomania is less severe than mania, which can result in reckless behavior and poor judgment.
  2. Duration of Mood Episodes. Compared to unipolar depression, bipolar disorder’s depressive episodes typically continue longer. Manic or hypomanic phases of bipolar disorder are also frequently shorter than depressed episodes.
  3. Genetic Factors. Although there is a hereditary component to both disorders, bipolar disorder has a stronger genetic connection. In comparison to unipolar depression, your risk of getting bipolar disorder is significantly increased if your family has a history of the condition.
  4. Severity of symptoms. Extreme mood swings associated with bipolar disorder can cause more severe disruptions in a person’s life and have a distinct impact on relationships, career, and general functioning.
  5. Treatment Approaches. There are various treatment modalities. While psychotherapy and, in some situations, medication, can help both disorders, bipolar disorder frequently necessitates the use of certain mood stabilizers to control manic or hypomanic episodes.

It is crucial to remember that a mental health professional must do a complete evaluation in order to diagnose and distinguish between these disorders. People who think they might have either ailment should have a proper evaluation so they can get a proper diagnosis and the right care.

What is Seasonal Depression and is it Genetic?

Seasonal Affective Disorder (SAD), often referred to as seasonal depression, is a type of depression that follows a seasonal pattern. It frequently happens during certain seasons of the year, most frequently in the fall and winter when there are fewer daylight hours. Although less frequently, some people may have SAD in the spring and summer.

Low mood, loss of interest in activities, exhaustion, changes in sleep and appetite, difficulties focusing, and feelings of worthlessness or hopelessness are just a few of the symptoms that SAD and major depressive illness share. But what distinguishes SAD is its predictable pattern of onset and remission depending on the cyclical nature of the seasons.

Research suggests that there is a genetic component to seasonal affective disorder, although the genetic links are not as well-established as they are for some other types of depression. Studies have shown that individuals with a family history of mood disorders, including SAD, might be at a higher risk of developing the condition themselves.

It’s crucial to remember that, although genetics may play a part in a propensity for SAD, environmental circumstances can have a big impact. It is believed that one of the main causes of SAD is diminished exposure to natural sunlight during particular seasons. Incorrect levels of neurotransmitters like serotonin and melatonin can cause circadian cycles to be disrupted, which can affect mood and sleep.

Seasonal affective disorder is more common in people with bipolar disorder. Mania episodes in some bipolar patients may be connected to a particular season. For instance, spring and summer might trigger mania symptoms or a milder type of mania (hypomania), as well as worry, agitation, and impatience. They could also go through periods of depression in the fall and winter.

Can SAD be treated? Much like other types of depression, SAD has varying treatment options. Experts believe that focusing on addressing the disruption in sleeping patterns and increasing the body’s exposure to natural light may help treat or manage SAD. Some of the more common treatments include:

  • Light Therapy. Phototherapy, another name for light therapy, entails exposure to glaring artificial light that mimics the effects of natural sunlight. The symptoms of SAD are frequently improved by this therapy.
  • Psychotherapy. People can learn coping mechanisms for controlling SAD symptoms with the aid of cognitive-behavioral therapy (CBT) and other talk therapies.
  • Medication. Antidepressant drugs may occasionally be recommended in order to treat SAD symptoms.
  • Lifestyle Changes. Getting regular exercise, eating well, and controlling stress can all help with mood enhancement and SAD symptom management.

Symptoms

Major Depression Disorder

Postpartum Depression

Bipolar Disorder

Seasonal Depression

Anxiety

Yes

Yes

Yes

Yes

Feelings of Isolation

Yes

Yes

Yes

Yes

Manic Episodes

No

No

Yes

Possible

Changes in Sleep Patterns

Yes

Yes

Yes

Yes

Change in Appetite

Yes

Yes

Yes

Yes

Exhaustion or Fatigue

Yes

Yes

Yes

Yes

Guilt

Yes

Yes

Yes

Yes

Dissociation 

Possible

Possible

Yes

Possible

Which Is the Strongest Genetic Link Associated with Depression?

According to research, the neurological underpinnings and pathogenesis of depressive illnesses are still unclear, despite extensive research over the past few decades. Based on family, twin, and adoption studies, genetic variables play significant roles in the onset of MDD and may provide crucial insights into the disease’s pathophysiology. 

While there isn’t a single “strongest” genetic link connected to depression, scientists have discovered a number of genetic markers and candidate genes that are thought to contribute to its onset. It’s crucial to remember that no single gene can entirely explain depression, which is likely affected by a mix of several genetic variants. 

However, the most studied single nucleotide polymorphisms (SNPs) are SNP rs782212 (gene: Intergenic), SNP rs4810896 (gene: LOC105372648-ARFGEF), and SNP rs7973260 (gene: KSR2). The most prevalent form of genetic variation in people is called an SNP. They entail a single nucleotide alteration at a specific location in the genome’s DNA sequence. These differences are what give people their unique characteristics, and they also have an impact on different traits, illnesses, and susceptibilities.

Intergenic Gene (SNP rs782212). SNP rs782212 is situated in an area of the genome that does not code for a particular protein, which is referred to as an “intergenic” region of DNA. Although research has demonstrated that intergenic areas can still perform regulatory roles, altering the expression of nearby genes or contributing to the three-dimensional folding of chromosomes, they were previously thought to be non-functional and were not given much attention. Numerous genetic variations for major depressive disorder (MDD) have been discovered through genome-wide association (GWA) research, however, the majority of these variations are intergenic. The intergenic regions have been shown to contain about 54% of long non-coding RNAs (lncRNAs). 

LOC105372648-ARFGEF Gene (SNP rs4810896). The gene identification LOC105372648-ARFGEF has a long non-coding RNA (lncRNA) component and a mention of the “ARFGEF” gene. A family of RNA molecules known as long non-coding RNAs (lncRNAs) are those that are longer than 200 nucleotides yet do not code for proteins. Instead, they participate in a number of cellular regulatory processes including chromatin remodeling, gene expression regulation, and interaction with other cellular elements. Some lncRNAs have been linked to particular illnesses and cellular functions. ADP-ribosylation factor guanine nucleotide-exchange factor (ARFGEF) is a protein that is encoded by the “ARFGEF” gene. ADP-ribosylation factors (ARFs), which are GTPases that participate in intracellular membrane trafficking and vesicle formation, are regulated by this protein. By enabling the exchange of GDP for GTP, ARFGEFs activate ARFs, and as a result, regulate their activity.

KSR2 Gene (SNP rs7973260). Obesity and metabolic characteristics are linked to the KSR2 gene and the SNP rs7973260. On chromosome 12, the KSR2 (Kinase Suppressor of Ras 2) gene produces a protein that participates in intracellular signaling pathways. KSR2 is a component of the Raf-MEK-ERK pathway, which plays a crucial role in the communication of signals from cell surface receptors to the cell nucleus, ultimately influencing functions like cell proliferation, differentiation, and survival. The KSR2 gene contains the single nucleotide polymorphism (SNP) rs7973260. SNPs, such as rs7973260, are variations in the DNA sequence that may affect how a gene functions or how it is expressed. Some SNPs have links to specific traits, illnesses, or drug reactions.

Regardless of genetic markers, anyone can experience depression, and most people may experience depression at least briefly in their lifetimes. If you think you have a unique genetic makeup that is susceptible to depression, a DNA test is your best bet. Experts believe that while Major Depressive Disorder (MDD) is yet to be scientifically proven to be hereditary, there are similar mental health conditions to MDD that are passed down from one generation to the next. 

If you want to take genetic testing for mental well-being, LifeDNA can give you insights into genetic inclination towards depression, loneliness, and other unique traits based on your DNA. Check out our personalized DNA plans to learn more.

Neuroticism: Are Personality Traits Genetic?

Aside from depression, one other important trait that can impact your well-being is Neuroticism. Neuroticism is one of the Big Five personality traits. It is a long-term and relatively stable tendency to be in a negative or anxious emotional state, especially in response to threats, frustration, or loss.  

Individuals who score high in this trait tend to experience mood swings, anxiety, irritability, and sadness. Neuroticism can also be damaging to the quality of your life and reduce your lifespan.

Depending on your DNA, you may have an increased likelihood of being moody and experiencing feelings such as anxiety, worry, fear, anger, frustration, envy, jealousy, guilt, depression, and loneliness. 

Get your mental health DNA test today for Neuroticism and unlock LifeDNA’s Personality & Cognition Report. 

LifeDNA’s Personality & Cognition Report - A Walkthrough

If you or a loved one are struggling with mental wellness challenges, consider exploring the potential benefits of genetic testing. 

By gaining a deeper understanding of your unique genetic makeup, you can better understand your genetic inclination towards mental wellness issues, and ultimately, make more informed decisions about your well-being. 

Take charge of your mental wellness journey today and see what genetic testing can do for you.

Explore LifeDNA's Personality Report

Summary

  • Depression or Major Depressive Disorder (MDD) is a common and serious medical illness that negatively affects how you feel, think, and act. 
  • Depression has a genetic component. People who have experienced depression in their families may be more likely to experience it themselves. 
  • MDD manifests in a variety of ways. There are several types of depression and some of have symptoms that overlap. 
  • There is no single genetic link that is solely connected to depression. Scientists have discovered a number of genetic markers and candidate genes that are thought to contribute to the onset of this mental condition. 
  • No single gene can entirely explain depression. Depression is likely affected by a mix of several genetic variants. 
  • Mental health professionals must do a complete evaluation of an individual potentially diagnosed with MDD  in order to assess and correctly treat the patient.

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports and suggestions do not diagnose or treat any health conditions or provide any medical advice. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results.

References

  1. https://www.psychiatry.org/patients-families/depression/what-is-depression
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065213/
  3. https://med.stanford.edu/depressiongenetics/mddandgenes.html
  4. https://pubmed.ncbi.nlm.nih.gov/33778956/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369539/
  6. https://www.nimh.nih.gov/health/publications/seasonal-affective-disorder
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138666/
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077049/#:~:text=The%20serotonin%20transporter%20gene%20and,MDD%20%5B17%E2%80%9319%5D

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

Can Genetic Data Improve Statin Prescription?

Catherine on May 13, 2025

Close-up of a statin pill, representing the role of genetic data.

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Statins are among the most widely prescribed drugs globally. Statins are used to lower blood cholesterol levels and reduce the risk of cardiovascular disease. Despite their broad usage and proven efficacy, not everyone responds to statins in the same way. Genetic differences among individuals play a key role in determining how well statins work, how they are metabolized, and the risk of side effects. Understanding the genetic response to statins is a step toward more personalized and effective treatments for cardiovascular health.

How Statins Work

The primary goal of statins is to reduce blood cholesterol levels.

 

Cholesterol is made in the liver through a step-by-step chemical process that starts with a molecule called acetyl-CoA. Acetyl-CoA comes from the breakdown of fats and sugars. These molecules are combined and processed through a pathway called the mevalonate pathway. 

 

A key step in this process is controlled by an enzyme called HMG-CoA reductase. HMG-CoA reductase helps convert acetyl-CoA into mevalonate. Mevalonate is an early form (precursor) of cholesterol. From there, the body goes through several more steps to finally produce cholesterol. Cholesterol is an important component of cell membranes- the outermost layer of our cells. Cholesterol is also the starting point to make hormones, like testosterone and estrogen, and vitamin D.

However, as we all know by now, excess cholesterol, especially in the form of  low-density lipoprotein (LDL) cholesterol, often called “bad cholesterol,” can build up in the walls of your arteries over time. This buildup forms plaques that narrow the arteries and make them stiff. This condition is called atherosclerosis. If a plaque breaks open, your body treats it like an injury and sends platelets to the area. The platelets form a clot. This clot can block blood flow and lead to a heart attack or stroke. So, while cholesterol is essential for your body, having too much of it in the wrong places can seriously increase the risk of cardiovascular disease.

Statins function by inhibiting HMG-CoA reductase. By blocking this enzyme, statins reduce levels of LDL. Lowering LDL levels helps prevent the buildup of plaques in arteries, thus reducing the risk of heart attack and stroke.

Analyzing the Genetics

Several genetic studies have reported that around 9% of the treatment effect of statins can be explained by genetic variations. Several genetic markers have been shown to influence our response to statins. 

SLCO1B1 

The SLCO1B1 gene encodes a liver transporter protein. This protein helps statins enter liver cells where they exert their effect. A common variant, SLCO1B1 c.521T>C (rs4149056), reduces the function of this transporter, leading to increased blood levels of statins like simvastatin. Increased levels of statin in the blood can heighten the risk of statin-associated muscle symptoms (SAMS), including myopathy and, rarely, rhabdomyolysis.

 

A 2012 case-controlled study researchers studied over 5,000 older adults who took either statin pravastatin or a placebo for about three years. They focused on specific gene variations in LXRA and SLCO1B1. They found that the  SLCO1B1 variant rs4149056-C, was also linked to a weaker response to the drug. And people with this variant had a smaller drop in LDL cholesterol compared to those without it. 

CYP3A5

This gene encodes an enzyme that is involved in the metabolism of statins like atorvastatin, simvastatin, and lovastatin. Variations in this gene can alter how quickly statins are cleared from the body. Reduced-function alleles (such as CYP3A5*3) can result in higher plasma statin concentrations, increasing the risk of side effects but potentially enhancing efficacy.

 

A 2021 systematic review analyzed data from eight studies involving 1,614 patients to examine whether the specific genetic variation CYP3A5*3, is linked to a reduced enzyme function and increased statin levels in the blood. The analysis found that individuals with the CYP3A5 *3/*3 genotype had a 1.4 times higher risk of experiencing statin-related side effects compared to those with other genotypes. 

ABCG2

The ABCG2 gene encodes a transporter protein involved in drug clearance from the body. The rs2231142 (Q141K) variant is associated with higher statin concentrations in plasma, especially rosuvastatin, and may influence both efficacy and side effect profiles.

 

A 2024 systematic review analysed 15 studies involving over 34,000 people found that a specific genetic variant, the A-allele of ABCG2 rs2231142, affects cholesterol levels and statin response. People with this variant tend to have lower “good” HDL cholesterol and higher “bad” LDL and total cholesterol. However, in Asian individuals with high cholesterol (dyslipidemia), this same variant makes the statin rosuvastatin work more effectively at lowering lipid levels. The study suggests that this genetic difference has the most impact in Asian populations and that using rosuvastatin preventively in those with the variant could help lower the risk of developing coronary artery disease.

Statin Intolerance

Statin intolerance refers to the inability to tolerate statin medications, usually due to side effects that make continued use difficult or impossible. The most common symptoms are muscle-related, such as pain, weakness, or cramps (known as statin-associated muscle symptoms or SAMS). In some cases, people may also experience liver enzyme abnormalities, digestive issues, or headaches. It often leads to patients stopping the medication or reducing the dose, which may increase their risk of heart disease if cholesterol levels are not well managed by other means.

 

Genetic testing, particularly for SLCO1B1 variants, is being increasingly used to predict the risk of statin-associated side effects. For example, a 2023 study showed that people with the SLCO1B1 c.521C/C genotype are more likely to have problems with simvastatin.

 

The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides guidelines for tailoring statin therapy based on SLCO1B1 genotype.

Toward Personalized Statin Therapy

Pharmacogenomic testing isn’t yet standard for all statin prescriptions, but its utility is growing. Patients with a history of side effects or those requiring high-intensity therapy could particularly benefit. Integrating genetic data with clinical information, such as age, liver and kidney function, and other medications, can help clinicians make more informed choices about which statin to prescribe, at what dose, and with what monitoring.

Conclusion

The genetic response to statins is a compelling example of how genomic insights can refine and personalize medicine. Variants in genes such as SLCO1B1, CYP3A4, CYP3A5, and ABCG2 can significantly influence how patients metabolize and respond to statins, affecting both efficacy and safety. As pharmacogenomic tools become more accessible and cost-effective, they are likely to become an integral part of routine cardiovascular care—ensuring that the right patient gets the right statin at the right dose.

References

  1. https://www.cell.com/cell-genomics/fulltext/S2666-979X(24)00351-3
  2. https://www.sciencedirect.com/science/article/abs/pii/S0021915011009348
  3. https://link.springer.com/article/10.1186/s12872-024-03821-2
  4. https://www.mdpi.com/2075-4426/11/7/677
  5. https://journals.lww.com/jpharmacogenetics/fulltext/2023/09000/Real_world_pharmacogenetics_of_statin_intolerance_.2.aspx
  6. https://cpicpgx.org/guidelines/cpic-guideline-for-statins/

Understanding Aortic Stenosis: The Aging Heart

Catherine on May 12, 2025

A detailed visual illustration of the human heart focusing on the aortic valve, showing the narrowing associated with aortic stenosis.

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

Overview

As we age, certain changes inside the heart can quietly affect how well it pumps blood. These changes often go unnoticed until they begin causing symptoms or are discovered during routine checkups. In some cases, they result from health issues that develop in middle age or from rare conditions present at birth.

One common issue that can arise from these hidden changes is the narrowing of one of the heart’s main valves. This narrowing puts extra strain on the heart, making it harder to pump blood to the rest of the body. Over time, this may lead to symptoms like shortness of breath, fatigue, chest pain, or more serious complications. Understanding what causes Aortic Stenosis and how it progresses is key to managing it effectively.

What Is Aortic Stenosis?

Aortic stenosis (AS) is when the aortic valve, one of the main valves in your heart, becomes narrowed or stiff. Normally, this valve opens and closes with every heartbeat, letting blood flow from the left side of the heart (left ventricle) into the aorta, which carries blood to the rest of the body.

In AS, the valve doesn’t open fully. This makes it harder for the heart to pump blood through it. Over time, the heart has to work harder to push blood out, which can lead to heart muscle thickening, fatigue, shortness of breath, and eventually heart failure if not treated. AS can happen for different reasons, including birth defects or age-related wear and tear. That’s why physicians say it can be either congenital (from birth) or acquired (developed later in life).

Types of Aortic Stenosis

Congenital Aortic Stenosis: This type is something people are born with. The most common cause is called a bicuspid aortic valve, where the valve has only two flaps (cusps) instead of three. Because of this unusual shape, the valve can become stiff and narrow earlier in life. There is an even rarer condition having a valve with only one flap, and this usually causes even more serious problems and symptoms at a younger age.

Acquired Aortic Stenosis: This type usually happens as people get older. It occurs when a normal valve with three flaps slowly becomes stiff and narrow because of calcium building up on it. This process is often caused by aging and lifestyle factors like high blood pressure, high cholesterol, and smoking.

Symptoms of Aortic Stenosis

Aortic stenosis (AS) may often go unnoticed for many years because early on, the narrowing valve may not cause any obvious problems. However, as the valve becomes more restricted, symptoms typically start to appear, especially during physical activity. Common signs to watch for include:

  • Shortness of breath during activity: The narrowed valve limits the amount of oxygen-rich blood reaching the body, making it harder to breathe when moving or exercising.
  • Chest pain or pressure (angina): The heart must work harder to push blood through the tight valve, which can cause discomfort or pain in the chest.
  • Fatigue and low energy: With less blood being pumped out, the body receives less oxygen, leading to feelings of tiredness and weakness.
  • Dizziness or fainting (syncope): Reduced blood flow to the brain during exertion can cause lightheadedness or fainting spells.
  • Heart palpitations or irregular heartbeat: As the heart tries to compensate for the restricted blood flow, abnormal heart rhythms may develop.

These symptoms often signal that aortic stenosis has progressed to a moderate or severe stage. If left untreated, severe AS can become life-threatening, especially once symptoms appear. Early recognition and medical evaluation are crucial to managing the condition effectively.

What Causes Aortic Stenosis Diagnosed?

Aortic stenosis happens when the valve that controls blood flow from your heart to the rest of your body becomes narrow or stiff. This narrowing makes it harder for your heart to pump blood, which may lead to symptoms and heart problems.

There are several reasons why this valve may become damaged or narrowed over time. Understanding these causes helps explain how aortic stenosis develops and why it affects some people more than others:

  • Born With Valve Problems: Some people have heart valves that didn’t form normally before birth. For example, instead of having three flaps (cusps), their valve might have only two or even one. This can cause the valve to wear out faster and narrow earlier in life.

  • Calcium Buildup with Age: As people get older, calcium can slowly build up on the valve, making it stiff and less able to open fully. This is the most common cause in adults over 65.

  • Damage from Infections: If infections like strep throat or scarlet fever aren’t treated, the bacteria can travel to the heart valves and damage them due to a condition called rheumatic fever . The body’s immune system tries to fight the infection but ends up damaging the valve, causing it to become narrow many years later.

  • Other Health Conditions: Some rare diseases like Paget’s disease (which affects bones), kidney failure, and inherited conditions that cause high cholesterol can also harm the valve. Autoimmune diseases like lupus and rheumatoid arthritis may cause inflammation that damages the valve too.

  • Age-Related Calcification: As people age, calcium, a mineral that helps build strong bones and may build up on the aortic valve. This calcium buildup causes the valve to stiffen and lose flexibility. When the valve can’t open fully, less blood passes through, so the heart must work harder. This process is the most common cause of aortic stenosis in older adults.

  • Rheumatic Fever: This is a rare complication from untreated strep throat or scarlet fever infections. It causes inflammation and scarring in the heart valves, including the aortic valve. The scarring thickens the valve and prevents it from opening properly. While less common today in many countries, rheumatic fever still causes aortic stenosis in some parts of the world.

  • Lifestyle and Health Risks: High blood pressure, smoking, and high cholesterol can injure your heart valves and blood vessels over time, making the valve wear out faster, especially as you age.

Genetics on Aortic Stenosis 

The congenital bicuspid aortic valve (BAV), a common congenital heart valve condition where the valve has two flaps instead of three, is highly genetic, with heritability estimated as high as 89%. However, this condition is not caused by just one gene but likely involves multiple genes and environmental factors.

Research has identified mutations in several important genes linked to BAV, such as NOTCH1, which is involved in valve development and calcification, and the GATA family of genes (GATA4, GATA5, GATA6), which also influence valve formation. Mouse studies show that altering these genes affects valve development and can cause BAV or related heart problems.

BAV changes the blood flow through the valve, creating abnormal stress that causes early calcium buildup and valve stiffening, which can lead to aortic stenosis (AS) and enlargement of the aorta. This calcification is an active process, similar to bone formation, involving cells in the valve turning into bone-like cells. The abnormal blood flow in BAV patients causes increased wall stress in the aorta, which differs based on the specific BAV subtype, leading to variations in how quickly calcification and valve disease develop.

Apart from BAV, acquired AS occurs later in life, mostly due to age-related calcium buildup on a normal valve and other cardiovascular risk factors like smoking, high cholesterol, and high blood pressure. This degenerative calcification is complex and likely requires multiple risk factors to cause significant valve damage.

Simply lowering cholesterol may not be enough to stop or reverse valve damage once it has progressed, highlighting the need for more personalized and combination therapies.

How Is Aortic Stenosis Diagnosed?

Diagnosing aortic stenosis usually starts when a doctor hears a heart murmur during a routine check-up. A murmur is an unusual sound made by blood flowing through a narrowed valve.

To confirm the diagnosis and understand how severe the stenosis is, doctors use several tests, including:

  • Echocardiogram: This is the most important test. It uses sound waves to create moving images of the heart and valve. It shows how well the valve is opening and how much blood is flowing through it.
  • Electrocardiogram (ECG or EKG): This test records the electrical activity of the heart and helps check for any irregular heartbeats or signs of heart strain.
  • Chest X-ray: This can show if the heart is enlarged or if there is fluid buildup in the lungs due to heart problems.
  • Cardiac catheterization: In some cases, a thin tube is inserted into a blood vessel and guided to the heart to measure blood pressure inside the heart chambers and valves. This gives detailed information about valve function.
  • CT scan or MRI: These imaging tests can help when more detailed pictures of the heart and valve are needed.

Early diagnosis is important because it helps doctors monitor the condition and decide when treatment may be needed to prevent serious complications.

How is Aortic Stenosis Treated? 

Treatment depends on how serious the narrowing is and whether you have symptoms.

  • Monitoring Without Symptoms:  If your aortic stenosis isn’t causing any symptoms, your doctor may just want to keep an eye on it. This means regular checkups and tests to watch for any changes.
  • Medications: For mild cases or to help with symptoms, doctors might prescribe medicines. These can include blood thinners to prevent clots, diuretics to reduce fluid buildup, or medicines for high blood pressure or irregular heartbeats. However, medications do not fix the valve or stop the narrowing from getting worse, they just help manage symptoms.
  • Valve Repair: If the valve damage is limited, your doctor might suggest repairing it. This can be done through surgery where the doctor opens your chest to fix the valve directly. Another option is balloon valvuloplasty, where a small balloon is inserted through a blood vessel and inflated to widen the valve opening. This may improve symptoms but is usually a temporary solution until a valve replacement is performed.

 

References

Is Aortic Stenosis Hereditary?

Catherine on May 11, 2025

Diagram of human body with heart highlighted to show where aortic stenosis occurs.

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

Overview

As people live longer, heart-related conditions are becoming more common and more serious. Among them is a disease that often goes unnoticed until it’s advanced, yet it’s one of the most frequent reasons older adults need heart valve surgery. 

It tends to affect men more than women, and its risk increases sharply with age, impacting over 2% of people above 60, and nearly 10% of those over 80. This condition is called aortic stenosis, where a narrowing of the heart’s main valve restricts blood flow and forces the heart to work harder.

It may be present at birth or develop gradually over time due to calcium buildup. Without treatment, especially after symptoms begin, the outlook may  be life-threatening, with up to half of untreated patients dying within two years. While surgery may help, it isn’t without risks, and there are still no medications proven to slow or stop the disease. That’s why researchers are urgently working to better understand aortic stenosis and find safer, more effective ways to treat it.

What Is Aortic Stenosis?

Aortic stenosis is a heart condition where the aortic valve becomes too narrow. This valve acts as a gateway, allowing blood to flow from the heart to the rest of the body. When the opening is too tight, it makes it harder for blood to pass through.

Because of this, the heart has to pump much harder to move blood forward. Over time, this extra effort can strain the heart and affect how well it functions. Aortic stenosis can be present at birth or develop later in life, often due to calcium buildup on the valve.

Symptoms of Aortic Stenosis

Aortic stenosis (AS) may develop slowly over time, and many people may not notice any symptoms in the early stages. However, as the valve becomes more narrowed and the heart struggles to pump blood effectively, symptoms can begin to appear, especially during physical activity. These signs often suggest that the condition has become moderate to severe.

Here are the most common symptoms and what they mean:

  • Shortness of breath: When the valve is too narrow, it limits how much oxygen-rich blood can reach the body during movement or exercise. This can make even simple tasks feel exhausting and cause you to feel out of breath quickly.
  • Chest pain or pressure: The heart must work much harder to push blood through the tight valve. This increased effort can reduce blood flow to the heart muscle itself, leading to pain, tightness, or pressure in the chest.
  • Fatigue: With less blood being pumped out to the body, your muscles and organs don’t get the oxygen and nutrients they need. This can leave you feeling unusually tired, even after light activity or rest.
  • Dizziness or fainting: During exertion, the narrowed valve may not allow enough blood to reach the brain. This can lead to lightheadedness or fainting spells, which are serious warning signs that the heart is under strain.
  • Heart palpitations or irregular heartbeat: As the heart struggles to keep up with the body’s needs, it may beat irregularly or feel like it’s racing or fluttering. This is the heart’s way of trying to compensate for the restricted blood flow.

These symptoms are signs that the heart is under stress. If left untreated, severe aortic stenosis can be life-threatening, especially once symptoms appear. That’s why early detection and proper management are so important.

What Causes Aortic Stenosis?

1. Congenital Causes

Some people are born with aortic stenosis. This type accounts for about 3% to 6% of all heart problems present at birth. The narrowing that blocks blood flow from the heart can occur in different areas, below the valve (subvalvar), at the valve itself (valvar), or just above it (supravalvar).

 In many cases, children with aortic stenosis also have other heart defects, such as a patent ductus arteriosus (a blood vessel that stays open after birth), aortic coarctation (a narrowed part of the aorta), or a ventricular septal defect (a hole between the heart’s lower chambers). These additional heart problems are found in about 15% to 20% of children with aortic stenosis.

 A common related condition is bicuspid aortic valve, where the valve has only two flaps instead of the usual three. In newborns, severe narrowing can lead to critical aortic stenosis, where blood flow to the body becomes dangerously low. This is a medical emergency that requires urgent treatment. In older children and teens, aortic stenosis or bicuspid aortic valve may cause few or no symptoms, but there is still a risk of sudden death if the valve narrowing is moderate to severe, even if the person feels completely fine.

2. Genetic Factors

Aortic stenosis, particularly when caused by BAV, often runs in families. Studies show that up to 89% of BAV cases are inherited, although no single gene explains it entirely. Instead, many genes likely play a role, often in combination. Some of the key genes linked to valve development include:

  • NOTCH1 – Mutations in this gene are associated with BAV and aortic aneurysms.
  • GATA4, GATA5, and GATA6 – These genes help guide early valve formation, and their mutations can cause valve malformations and calcification.
  • Nkx2.5 – Works with GATA genes to support heart development and may contribute to valve disease when altered.

These genes affect how the valve forms in the womb. When disrupted, they can lead to long-term problems such as BAV, valve narrowing, and associated conditions like aortic dilation.

3. Age-Related and Degenerative Causes

In people over 75, aortic stenosis is usually by age-related wear and tear. It affects over 25% of those over age 65 and becomes more severe with age. The most common cause in older adults in developed countries is calcification from aging, not rheumatic disease. Several health and lifestyle factors increase the risk of age-related AS:

  • High LDL (bad) cholesterol:  LDL stands for low-density lipoprotein. It carries cholesterol through your blood, but too much of it can build up in your arteries and heart valves. This buildup contributes to hardening and narrowing, including in the aortic valve.
  • Smoking:  Smoking damages blood vessels and increases inflammation in the body. It speeds up the aging and calcification of the aortic valve, while also raising the risk of heart disease in general.
  • High blood pressure (hypertension):  When your blood pressure is too high, your heart has to work harder to pump blood. Over time, this extra pressure can wear out the aortic valve and promote stiffness or thickening of the valve tissue.
  • Diabetes or high blood sugar: Uncontrolled blood sugar levels can damage blood vessels and lead to inflammation. This can affect how the valve tissue repairs itself and may encourage calcium buildup on the valve.
  • Metabolic syndrome:  This is a group of conditions that often happen together, including high blood pressure, high blood sugar, excess belly fat, and abnormal cholesterol levels. Having metabolic syndrome raises your risk of heart disease and accelerates the calcification of the aortic valve.

How Is Aortic Stenosis Diagnosed?

Diagnosing aortic stenosis (AS) begins with a careful medical evaluation. Because symptoms can take years to appear—or may be mistaken for other conditions—doctors use a combination of physical exams and heart tests to confirm the diagnosis and understand how severe the narrowing is.

Here are the most common steps involved:

  • Physical examination: A doctor listens to your heart using a stethoscope. A heart murmur, which sounds like a whooshing or swishing noise, can be a sign of turbulent blood flow through a narrowed valve.
  • Echocardiogram (echo):  This is the most important test for diagnosing AS. It uses sound waves (ultrasound) to create images of the heart. It shows how well the valve is opening and how blood is moving through the heart.
  • Electrocardiogram (ECG or EKG):  This test measures the electrical signals in your heart. It can help detect signs of heart strain or thickening of the heart muscle caused by AS.
  • Chest X-ray:  A chest X-ray gives a picture of the heart and lungs. It can show if the heart is enlarged or if there’s fluid in the lungs, both of which may be related to AS.
  • Cardiac catheterization:  In some cases, especially before surgery, doctors may perform this test to get a detailed look at the heart and measure pressure inside the chambers. A thin tube (catheter) is inserted into a blood vessel and guided to the heart.
  • Exercise or stress testing: This test checks how the heart performs under physical stress. It’s often used when symptoms are unclear or to assess how well the heart tolerates activity.

These tests help doctors determine the severity of aortic stenosis and decide on the best treatment plan, whether it’s regular monitoring, medication for related conditions, or valve replacement.

References:

 

Is Aortic Valve Calcification Genetic?

Catherine on May 10, 2025

A highlighted image of the heart showing aortic valve calcification, focusing on calcium buildup in the aortic valve area.

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

The aortic valve is one of the heart’s key valves. It controls the flow of blood from the heart to the rest of the body. To do this job well, it needs to open and close smoothly with every heartbeat, about 100,000 times a day.

Over time, the valve’s structure may begin to change. In some people, this may even happen earlier than expected by a condition known as aortic valve calcification. When the valve becomes less flexible, it doesn’t open and close properly. This limits blood flow from the heart and forces the heart to work harder to pump blood through the narrowed valve.

Understanding how and why this happens is important not just for treating it, but for recognizing who may be at risk before serious complications develop. 

You may want to read: What Does Genetics Tell About Your Exercise Heart Rate Recovery?

What Is Aortic Valve Calcification?

Aortic valve calcification happens when calcium slowly builds up on the valve leaflets, causing them to stiffen and harden. Over time, this buildup can make the valve that would allow blood to leave the heart less flexible, often leading to a condition called aortic stenosis. Aortic valve calcification is more common in older adults, but some younger individuals may also develop it, raising the question of whether genetic factors are involved.

Symptoms of Aortic Valve Calcification

Often in the early stages, aortic valve calcification doesn’t cause any symptoms. Many people don’t realize they have it until the valve becomes more narrowed or stiff, which can affect how well the heart pumps blood.

As the condition progresses, these symptoms may appear:

  • Shortness of breath – You may feel like you can’t catch your breath, especially during exercise or when walking uphill. This happens because your heart has to work harder to push blood through the narrowed valve.
  • Chest pain or tightness – You might feel pressure, squeezing, or pain in your chest, especially when being active or under stress. This occurs when your heart doesn’t get enough oxygen-rich blood.
  • Fatigue or weakness – Everyday activities like climbing stairs or walking short distances might make you feel very tired or worn out. The body may not be getting enough blood and oxygen due to reduced heart function.
  • Dizziness or fainting – You may feel lightheaded or even pass out. This can happen because blood flow to the brain is reduced when the heart struggles to pump through a narrowed valve.
  • Irregular heartbeat or a racing heart – You might notice that your heart skips a beat, beats too fast, or feels like it’s fluttering. This is called an arrhythmia and can be caused by strain on the heart.

These symptoms usually develop slowly over time but should not be ignored. If you experience any of them, especially if you have a family history of valve problems it isimportant to talk to your doctor. Early diagnosis can lead to better care and help prevent complications.

What Causes Aortic Valve Calcification?

The exact cause of aortic valve calcification isn’t fully understood, but several factors are known to increase the risk. These include both biological processes and lifestyle influences:

  • Aging:  As we get older, calcium tends to accumulate in various body tissues, including the heart valves. Over time, this buildup can stiffen the aortic valve and affect its ability to open and close properly.
  • Chronic Inflammation:  Long-term inflammation in the body, often due to other underlying conditions or immune responses, may lead to damage and scarring in the valve tissue, creating an environment where calcium deposits can form more easily.
  • High Blood Pressure and High Cholesterol: Elevated blood pressure puts extra stress on the heart and valves, while high cholesterol can lead to fatty plaque buildup. Both can injure the valve, promoting calcification over time.
  • Kidney Disease: Kidney problems affect how the body balances calcium and phosphate. When this balance is off, it can lead to excess calcium in the blood, which may deposit on the valves.
  • Lifestyle Factors: Habits like smoking, a poor diet, and lack of physical activity contribute to vascular damage, inflammation, and poor heart health—all of which can increase the risk of valve calcification.

Despite these risk factors, some people still develop aortic valve calcification without any clear external cause, suggesting that genetic predisposition may also play a role.

Genetics on Aortic Valve Calcification

An early sizable genetic study provided strong evidence that aortic valve calcification (AVC) can be influenced by inherited factors. Conducted by researchers within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium, the study examined genetic data from thousands of participants to discover which genes might be linked to calcium buildup in heart valves.

Researchers looked at more than 6,900 individuals for signs of AVC and more than 3,700 for mitral annular calcification using CT scans. All participants were part of long-term population studies and were primarily of white European ancestry. Their findings were later confirmed in multiethnic groups, including African-American, Hispanic-American, and Asian-American cohorts.

A genetic variant called rs10455872 in the LPA gene , which affects lipoprotein(a), or Lp(a), levels, was strongly associated with aortic valve calcification. Individuals with this variant had more than twice the risk of developing AVC compared to those without it. This gene variant was also linked to clinical aortic stenosis (a severe narrowing of the aortic valve) and a higher likelihood of needing aortic valve replacement.

The role of the rs10455872 in AVC has further been confirmed in several recent studies including a GWAS study performed in almost 1 million participants. A total of 32 genomic loci were found to be associated with AVC in this recent study, of which 20 had not been previously discovered. The earlier study also identified two genetic variants near the IL1F9 gene, which is involved in inflammation, as potentially linked to calcification at mitral annular valve,  another heart valve that separates the left atrium and left ventricle. However, these findings were not consistently replicated, so more research is needed on the role of this proinflammatory gene. 

Research has consistently shown that genetics, especially variation in the LPA gene, plays a significant role in whether someone develops aortic valve calcification. While aging and lifestyle are important factors, some individuals may inherit a higher risk due to their genetic makeup.

Understanding this connection may help identify people at risk earlier, follow their heart health more closely, and eventually develop treatments that lower the lipoprotein(a) or stop its harmful effects.

Who Is at Higher Risk?

Aortic valve calcification can affect anyone, but some individuals are more likely to develop it due to age, genetics, or certain other health conditions. Knowing your risk can help you take preventive steps and talk to your doctor about screening, especially if you fall into one or more of these categories. Those at higher risk include:

  • Older Adults (Usually Over Age 65)
     As people age, calcium naturally accumulates in body tissues, including the heart valves. This age-related buildup is the most common cause of aortic valve calcification.
  • People with a Family History of Heart Valve Disease
     If close relatives have been diagnosed with aortic stenosis or other valve problems, you may be genetically predisposed to similar conditions.
  • Individuals with High Lipoprotein(a) Levels
     Lipoprotein(a), or Lp(a), is a type of cholesterol that can contribute to plaque and calcium deposits in blood vessels and valves. Elevated levels are often inherited and increase the risk of valve calcification.
  • Those with Genetic Syndromes Affecting the Heart
     Certain inherited conditions, such as bicuspid aortic valve or Marfan syndrome, can alter the structure or function of the heart and make calcification more likely at an earlier age.

Can You Prevent Aortic Valve Calcification?

While you can’t change your genes or stop the natural aging process, you can lower your risk of aortic valve calcification by taking care of your overall heart health. Here are practical ways to help protect your valves:

  • Eat a Heart-Healthy Diet: Focus on foods low in saturated fat, sodium, and added sugar. A diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats supports cardiovascular health and helps prevent calcium buildup.
  • Keep Cholesterol and Blood Pressure in Check:  High cholesterol and hypertension can damage your heart valves over time. Regular checkups, medication (if prescribed), and lifestyle changes can help keep these under control.
  • Avoid Smoking:  Smoking accelerates vascular damage, increases inflammation, and contributes to plaque and calcium buildup. Quitting smoking is one of the most effective ways to protect your heart and valves.
  • Stay Physically Active:  Regular exercise strengthens the heart, improves circulation, and supports healthy blood pressure and cholesterol levels. Aim for at least 30 minutes of moderate activity most days of the week.
  • Manage Diabetes or Kidney Disease:  Both conditions can affect how your body handles calcium and other minerals. Good management through medication, diet, and regular monitoring reduces the risk of calcification and other heart-related issues.

These healthy habits not only support heart valve function but may also slow the progression of existing calcification, helping you maintain better heart health for longer.

References



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