Groundbreaking international study links higher genetic risk of depression to women
A new, large-scale genetic analysis suggests that women carry a higher genetic risk for major depressive disorder than men. Published in Nature Communications, the study claims to be the largest to date examining how genetic factors differ between the sexes in depression. Researchers identified 16 genetic variants associated with depression in women and eight in men, with many variants shared across genders but a notable excess of risk regions in females.
What the study did and what it found
The research pooled data from five international cohorts across Australia, the Netherlands, the United States and the United Kingdom, totaling more than 400,000 participants. The final sample included 130,471 women and 64,805 men with major depression, plus 159,521 women and 132,185 men without the diagnosis. While many genetic variants linked to depression appeared in both sexes, the study found a higher burden of genetic risk in females, which researchers say could be due to female-specific variants.
Dr. Brittany Mitchell, a senior researcher at QIMR Berghofer Medical Research Institute, noted that the findings are consistent with the well-established pattern that women are about twice as likely as men to experience depression in their lifetimes. “We already know that females are twice as likely to suffer from depression in their lifetime than males,” she said. “And we also know that depression looks very different from one person to another. Until now, there hasn’t been much consistent research to explain why depression affects females and males differently, including the possible role of genetics.”
Biological insights and links to metabolic traits
The team reported stronger genetic correlations in women between depression and metabolic traits, such as body mass index and metabolic syndrome, than in men. Lead researcher Dr. Jodi Thomas highlighted that these genetic links may help explain why women with depression more often experience metabolic symptoms like weight changes or altered energy levels. “These genetic differences may help explain why females with depression more often experience metabolic symptoms,” she said.
Why this matters for diagnosis, treatment and future research
Experts emphasized that the study supports a multifaceted view of depression that accounts for biology alongside behavioral and environmental factors. The researchers cautioned that social and environmental explanations—such as under-diagnosis in men or higher exposure to violence in women—remain important. Still, the genetic evidence suggests that sex-specific biology plays a meaningful role in how depression develops and presents itself.
Prof. Philip Mitchell, though not involved in the study, commented that there has long been debate about why depression rates are higher in females. He noted that the study provides strong evidence that genetic factors contribute to this difference, with distinct regions of the genome implicated for each sex and limited overlap. This line of work could steer future research toward gender-tailored interventions and even different pharmacological approaches depending on sex-specific biological pathways that underlie depression.
Limitations and scope
The authors acknowledged limitations, including an analysis restricted to European populations, which may limit applicability to other groups. They also faced a gender imbalance in the sample, with roughly twice as many women with depression as men, though the team conducted additional analyses to mitigate this issue.
Implications for clinical practice and public health
With a growing understanding that depression is influenced by a constellation of factors, this study points toward more personalized strategies. If specific genetic regions tied to depression in women are validated by further research, there could be implications for early identification, prevention, and even sex-differentiated treatment approaches as science progresses. In the meantime, recognizing the higher genetic risk in women reinforces the importance of accessible mental health resources for all genders and continued investment in precision medicine for mood disorders.
