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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, which is estimated to affect one in five people in their lifetimes in the United States alone, poses an enormous public health challenge. It is characterized by frequent changes in mood, cognition, energy, sleep, and appetite, and can have profound impacts on the affected individual’s emotional state and social functioning.Â
Read our in-depth analysis of the Genetics of Depression.
While stressful life experiences, adversity in childhood, and chronic health problems are all known to elevate the risk of depression, genetic factors have always been suspected of playing a major role. Indeed, family and twin studies have long hinted that heritability can significantly affect whether someone is prone to this condition. In 2006, a twin study based on the Swedish Twin Registry reported the heritability of susceptibility to major depression at 42% for women and 29% for men, concluding that major depression was moderately heritable, confirming prior studies.
A recent large-scale genome-wide association study (GWAS) that is part of the even larger 23andMe study discussed here, uncovered hundreds of specific genetic variants linked to major depression risk, underscoring its polygenic nature. The variations associated with depression are often in genes that affect the neuronal signaling pathways and brain regions that govern mood regulation, reinforcing the notion that depression stems partly from disruptions in normal neurobiological processes.Â
Importantly, many studies have now shown that including diverse populations in research has exposed new genetic markers that would have otherwise gone undetected, providing a more accurate and equitable view of how genetic predispositions interact with life experiences in shaping,for example, the risk and presentation of depression.
Thecurrent large-scale study spearheaded by the University of Edinburgh and King’s College London, in collaboration with 23andMe, has mapped out an unprecedented number of genetic links to depression by examining more than five million people across 29 countries.Â
This study is particularly notable for including individuals not only with European ancestry, but also those with diverse ancestral backgrounds, such as African, East Asian, Hispanic, and South Asian. The study takes a notable step toward rectifying a long-standing bias in genetic research: the underrepresentation of non-European populations. In doing so, it offers new genetic discoveries and fresh perspectives on the underlying causes of depression and suggests new paths for therapeutic innovation.
One of the most striking outcomes of this project is the identification of nearly 300 previously undiscovered genetic variants that can increase susceptibility to depression. Of these variants, 100 were pinpointed specifically because researchers prioritized expanding representation beyond traditionally studied European ancestry groups. In total, almost 700 genetic variations linked to depression were mapped, implicating more than 300 individual genes. The final findings of this study have not yet been published in a scientific journal, but it will likely be beneficial to study the biological underpinnings of depression that are associated with the newly discovered genes and genetic variants.
This broad array of novel findings highlights the complexity of depression’s genetic architecture. It reminds us that a condition as widespread and multifaceted as depression is influenced by an equally complex set of molecular factors.
Beyond the identification of genetic variants, the study offers hints about potential therapeutic targets. Many of the genes implicated by these newly discovered variants are connected to neurons within brain regions involved in emotion regulation. These findings pave the way for more targeted approaches to treatment.Â
Notably, the current study highlighted certain existing medications, including pregabalin (used for chronic pain) and modafinil (used for narcolepsy), as potential candidates for repurposing to treat depression. Although further clinical research will be needed to confirm efficacy and safety, the notion that established drugs might be repurposed to tackle depression could expedite the development of new, more effective treatment modalities.
The collaboration with 23andMe illustrates how data from consumer-driven genetic testing can contribute to scientific research. By consenting to participate, the company’s diverse customer base provided a large dataset for studying genetic risk factors in complex diseases. This information helped identify new variants and validate polygenic risk scores (PRS) for depression across multiple ancestry groups. 23andMe now offers personalized depression risk reports, enabling individuals from different backgrounds to gain insights into their genetic predispositions. Such information may support earlier detection and intervention, potentially reducing the impact of depression.
Read our in-depth analysis of the 23andMe PRS reports.
It is important, however, to approach polygenic risk scores with caution. While knowing one’s genetic predisposition can be empowering, these findings do not constitute a definitive prediction of future mental health. Environmental factors, lifestyle choices, and an array of personal experiences still play pivotal roles in whether and how depression manifests. For many, seeing a potentially higher genetic likelihood for depression might serve as a reminder to maintain healthy coping strategies, seek preventive mental health services, or discuss any concerns with a healthcare professional.
Looking ahead, this landmark study opens up numerous avenues for continued research on depression. By continuing to build on large-scale, multi-ethnic genetic data, scientists will be able to refine our understanding of complex diseases like depression. They can also delve deeper into gene-by-environment interactions, investigating how genetic predispositions might combine with life experiences to heighten or mitigate risk. The ultimate objective of such work is not only to unlock the biological mechanisms behind depression but to develop novel, more precise treatments that cater to individuals’ genetic and environmental profiles.
The University of Edinburgh and King’s College London multi-national collaboration study with 23andMe represents a pivotal moment in depression research, exemplifying what can be achieved when genomic studies embrace diversity. It highlights the scientific and clinical potential of large-scale, inclusive datasets to transform our understanding of mental health conditions. As new findings from this research lineage emerge, they will undoubtedly help shape more personalized, equitable, and effective approaches to depression care worldwide.
