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Women may be nearly twice as likely to develop depression because of thousands of unique genetic variations, a large international study has found. Published recently in the journal Nature Communications, the research titled Sex-stratified genome-wide association meta-analysis of major depressive disorder reveals that while men and women share more than 7,000 gene variants linked to major depressive disorder (MDD), women carry an additional 6,000 that may explain their higher risk.
This means women’s genetic makeup places them under a heavier burden of risk, in addition to social and environmental stressors.
Researchers analysed genetic data from over 130,000 women and 65,000 men diagnosed with depression, alongside data from over 290,000 people without depression. Participants came from Australia, the Netherlands, the UK, and the US — making it the largest study of its kind.
The team compared genetic markers between sexes to see whether certain variants influenced depression differently in women and men.
What exactly are gene variants?
A gene variant is simply a change in the DNA sequence. Some variants are harmless, while others can raise the risk of illnesses, including depression. These variants can be inherited from parents or occur spontaneously.
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In women, thousands of these variants appear to interact with biological processes such as brain development, hormones, and metabolism, making them more vulnerable to depressive disorders.
Genetic factors explain why depression symptoms differ by sex
According to the study, women with depression are more likely to experience metabolic-related symptoms such as weight gain, sleep issues, and fatigue.
The researchers found that the genetic changes linked to women’s depression also overlap with traits related to metabolism and immune function. By contrast, men with depression more often display anger, aggression, or substance use — symptoms less tied to metabolic changes.
Depression-linked DNA differences are inherited, not acquired
Researchers emphasise that these are inborn DNA differences — not caused by trauma, lifestyle, or environment. However, environmental factors such as stress or discrimination can still trigger depression, especially in people with a genetic predisposition.
What does this mean for treatment?
The findings highlight the need for sex-specific approaches to diagnosing and treating depression. For example, treatments for women may benefit from targeting metabolic pathways, while therapies for men might focus on behavioural or neurocognitive patterns.
“Understanding how depression differs between sexes gives us a roadmap for more tailored and effective treatments,” the authors said.
The study provides one of the clearest genetic explanations yet for why women are more vulnerable to depression. Still, experts stress that depression results from a complex mix of genes, environment, and life experiences.
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This content is for informational purposes only and is not a substitute for professional medical advice.
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