Genetic Insights into Why Depression Affects Women More Than Men

       In a recent study done by Dr. Jodi Thomas at the School of Biomedical Sciences at The University of Queensland, it has been found that major depressive disorder (MDD) impacts almost twice as many women as it does men. Researchers findings in the study with over 200,000 men and women with MDD start to unpack the underlying causes of MDD in both sexes. They categorized genetic effects into three separate groups: shared effects present in both sexes, sex-dependent effects that differ in magnitude or direction, and sex-specific effects present in only one sex. Their analysis revealed that women carry about 13,200 genetic variants linked to MDD while men have only 7,100, suggesting that women might bear a higher genetic burden (including 6,100 variants potentially unique to females). Additionally, three genomic regions were identified as major only in women, supporting the presence of sex-specific genetic influences.

The study also focused on genetic correlations between MDD and metabolic traits like body mass index (BMI) and metabolic syndrome. These correlations were stronger in women, consistent with clinical observations that women with MDD more often experience metabolic symptoms. With this, researchers recorded limitations in statistical power, meaning that not all causal genetic regions could be definitively identified. In addition, genetic correlations between men and women with MDD were slightly lower than expected, underscoring possible differences in cohort characteristics. This suggests that twin studies and GWASs may capture distinct aspects of genetic risk.

    Ultimately, the study highlighted a noteworthy variant on the X chromosome in men, mapping to the IL1RAPL1 gene, which is involved in memory and has been associated with several other traits but not previously with MDD. While the role of this gene in male depression is still unclear, it provides a promising opportunity for further research. Overall, the study harps on the importance of sex-stratified analyses to comprehend the biological function of MDD and points to the need for more data collection and further investigation into molecular mechanisms that mediate sex-dependent and sex-specific genetic impacts.

Sources:

https://www.nature.com/articles/d41586-025-03374-0

https://www.nature.com/articles/s41467-025-63236-1

https://www.mayoclinic.org/diseases-conditions/depression/symptoms-causes/syc-20356007