Major Depression Breakthrough: Nearly 300 Previously Unknown Genes Discovered

We are closer than ever to accurately determining if a person’s biology makes them more prone to major depressive disorder. Researchers have identified 293 new gene variants linked to increased risk, a 42% increase from what was previously known.

A large trans-ancestry genome-wide association study (GWAS) analyzed the genetic data of 688,808 individuals with depression and 4,364,225 controls. The study identified 697 variants across 635 gene loci associated with the disorder, including 293 newly discovered variants.

This achievement is the culmination of nearly eight years of collaboration by an international team of scientists, led by the University of Edinburgh and King’s College London, alongside researchers from QIMR Berghofer, The University of Queensland (UQ), and the Brain and Mind Centre in Sydney.

“Our study has uncovered numerous genetic factors contributing to depression, highlighting its complex genetic basis,” said UQ scientist Enda Byrne. “These discoveries pave the way for better treatments and support for those affected by the condition.”

While depression arises from a complex interplay of biological and environmental factors, this comprehensive genetic risk map enables medical professionals to more easily identify patients predisposed to the condition.

Genetics and Depression

Last April, University of Sydney researchers Jacob Crouse and Ian Hickie emphasized the importance of understanding genetics in depression: “Consider two individuals—one with high genetic risk and one with low risk—who both lose their jobs. The genetically vulnerable person might perceive the loss as a threat to their self-worth and social status, feeling shame and despair, and avoiding the search for a new job out of fear of failure. In contrast, the other person might view the loss as less personal, attributing it to the company’s circumstances. These differing perspectives affect how they internalize and remember the event.”

Although this explanation simplifies a highly nuanced and personal condition, it illustrates the impact of genetic vulnerability. Individuals with a full complement of these identified variants face a significantly higher risk of developing depression. Recognizing those most biologically at risk allows for tailored support and more effective treatment options.

The study analyzed genetic data from 29 countries across 109 studies, with 24% of participants from non-European backgrounds, leading to the discovery of 100 novel genetic variants. It highlights the need for more research on depression in underrepresented African populations.

While a single genetic variant has minimal impact, multiple variants can significantly increase susceptibility. Researcher Brittany Mitchell emphasized the need for better insights to improve treatment and prevention.

Understanding depression’s genetic basis could enhance drug therapies, including repurposing medications for chronic pain or narcolepsy, and enable proactive interventions to help high-risk individuals manage stressors effectively.

Key gene variants were identified in loci DRD2, FURIN, and CYP7B1, linked to neuroinflammation, neurosteroid synthesis, and synaptic function. Of the 697 variants found, 308 were tied to postsynaptic density and receptor clustering, critical for neuronal communication.

Advancing Genetic Insights for Targeted Depression Treatments

This study advances understanding of the genetic basis of synaptic and neuronal dysfunction in depression, paving the way for targeted treatments. “Inclusive studies like this can improve treatments, reduce the condition’s global impact, and underscore the biological basis of mental health disorders,” said Brittany Mitchell.

Since the first genetic link to depression was discovered in 2011, research has strengthened the case for biology as a key factor in its risk and severity. DRD2, also linked to ADHD, Tourette’s, and PTSD, highlights the connection between dopamine signaling and attention, motivation, and impulsivity, crucial in depression and related conditions.

FURIN and CYP7B1 are believed to have a stronger link to depression and related neurodevelopmental conditions.

The study found that genetic factors account for approximately 37% of depression’s heritability, with the remaining 63% influenced by factors like stress, trauma, and lifestyle. Individuals with these risk variants have a 50% chance of passing them to their offspring. While this doesn’t guarantee that a child will develop depression, it raises their likelihood if other risk factors are also present.

Understanding these variants and their connection to depression, ADHD, and anxiety disorders can help reduce stigma, minimize misdiagnosis, and accelerate the development of more effective treatments.

Read the original article on: New Atlas

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