HQ Team
January 20, 2025: Research has unveiled 293 new gene variants linked to major depressive disorder (MDD), significantly enhancing our understanding of the genetic factors responsible for this complex condition. The findings represent a 42% increase in known genetic risk factors for MDD, bringing the total number of identified variants to 697 across 635 gene loci.
This research, conducted by an international team led by the University of Edinburgh and King’s College London, is part of a massive genome-wide association study (GWAS) involving 688,808 individuals diagnosed with depression and 4.3 million controls. The comprehensive analysis spanned nearly eight years and included participants from 29 countries, with 24% being from non-European backgrounds.
This diversity allowed researchers to discover approximately 100 novel variants not previously identified in European-centric studies, highlighting the need for further research into underrepresented populations, particularly those in Africa.
Genetic factors responsible for depression
According to UQ scientist Enda Byrne, “Our research has identified numerous genetic factors that contribute to the condition, showing that it involves a complex mix of genes.” This insight is crucial as it paves the way for personalized treatment approaches, enabling healthcare providers to better support individuals at higher genetic risk for depression.
The study emphasizes that while 37% of depression heritability can be attributed to genetic factors, the remaining 63% is influenced by environmental factors such as stress and trauma. This aligns with previous findings that suggest both genetic predispositions and life experiences play significant roles in the development of MDD.
Targetted therapies for depression
Traditionally, most antidepressants have focused on modulating monoamine neurotransmitters such as serotonin and norepinephrine. However, with the discovery of these new genetic variants, researchers can develop targeted therapies. For instance, variants associated with neuroinflammation and synaptic function. By identifying specific gene variants—such as those in loci like DRD2, FURIN, and CYP7B1, researchers can develop targeted therapies. This includes exploring existing medications for repurposing to treat depression more effectively.
Current antidepressants often take weeks to show therapeutic effects. Understanding the genetic basis of individual responses could lead to strategies that enhance the speed and effectiveness of treatment, possibly through combination therapies or by targeting specific receptors that modulate rapid neuroplasticity.
And, beyond medication, identifying individuals with a higher genetic risk of developing depression could be preemptively armed with specific techniques to better manage stressors – one of the many triggers of the condition.
As noted by Brittany Mitchell from QIMR Berghofer, who was a part of the research team, “While depression is a growing major health issue, we lack the insights needed to better treat and prevent it.” The newly identified genetic variants provide a clearer picture of how biological factors contribute to depression, potentially reducing stigma and improving diagnostic accuracy for related conditions like ADHD and PTSD.
The findings were published in the journal Cell.
