Study finds different genes linked to depression in males and females

The new findings are promising for developing sex-specific treatments for depression in the future.
Mert Erdemir
Depressed man stock image.
Depressed man stock image.


A new study conducted by researchers from McGill University, Canada, suggests that major depression is linked to different genes in males and females, according to an institutional press release.

Conducting a sex-stratified, genome-wide association analysis of data from over 270,000 individuals, the research team observed that sex-specific prediction methods were more precise in forecasting an individual's genetic susceptibility to developing depression than methods that did not specify sex.

147 genes significantly associated with broad depression

Depression is a complex psychological disorder that is twice as common in females than in males. It is also established that several genetic variants are associated with an increased risk of developing depression.

In relation, the new research identified 11 areas of DNA associated with depression in females and only one area in males. Plus, the study found 147 genes associated with depression, of which 64 were associated with depression in female subjects and 53 in males.

It was also revealed that depression was significantly associated with metabolic disorders and diseases in females, highlighting the importance of considering this aspect when treating women with depression. However, although the biological processes underlying depression are similar between males and females, the study found that different genes were involved in each sex.

"This is the first study to describe sex-specific genetic variants associated with depression, which is a very prevalent disease in both males and females. These findings are important to inform the development of specific therapies that will benefit both men and women while accounting for their differences," says Dr. Patricia Pelufo Silveira, lead author of the study and Associate Professor in the Department of Psychiatry.

"In the clinic, the presentation of depression is very different for men and women, as well as their response to treatment, but we have very little understanding of why this happens at the moment."

These findings are specifically promising for developing sex-specific treatments for depression in the future.

The study was published in Molecular Psychology.

Study abstract:

There are marked sex differences in the prevalence, phenotypic presentation, and treatment response for major depression. While genome-wide association studies (GWAS) adjust for sex differences, to date, no studies seek to identify sex-specific markers and pathways. In this study, we performed a sex-stratified genome-wide association analysis for broad depression with the UK Biobank total participants (N = 274,141), including only non-related participants, as well as with males (N = 127,867) and females (N = 146,274) separately. Bioinformatics analyses were performed to characterize common and sex-specific markers and associated processes/pathways. We identified 11 loci passing genome-level significance (P < 5 × 10−8) in females and one in males. In both males and females, genetic correlations were significant between the broad depression GWA and other psychopathologies; however, correlations with educational attainment and metabolic features, including body fat, waist circumference, waist-to-hip ratio, and triglycerides, were significant only in females. Gene-based analysis showed 147 genes significantly associated with broad depression in the total sample, 64 in the females and 53 in the males. Gene-based analysis revealed “Regulation of Gene Expression” as a common biological process but suggested sex-specific molecular mechanisms. Finally, sex-specific polygenic risk scores (PRSs) for broad depression outperformed total and the opposite sex PRSs in the prediction of broad major depressive disorder. These findings provide evidence for sex-dependent genetic pathways for clinical depression as well as for health conditions comorbid with depression.

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