It is widely reported that depression is more common in women than men, and women are twice as likely to be diagnosed as men. A new sex-specific study from McGill University found that there are differences between male and female genes and how they relate to depression.
In a study of more than 270,000 people, researchers found that sex-specific prediction methods were more accurate in predicting an individual’s genetic risk of developing depression than prediction methods that did not specify sex. The researchers found 11 areas of DNA that were linked to depression in women and only one area in men.
They also found that depression was specifically linked to metabolic diseases in women, an important aspect to consider when treating women with depression. Although the biological processes involved in depression are similar in men and women, the researchers found that different genes were involved for each sex. This information may be useful in identifying future sex-specific treatments for depression.
"This is the first study to describe sex-specific genetic variants associated with depression, which is a highly prevalent disease in both men and women. These findings are important to inform the development of specific therapies that will benefit both men and women." while taking into account their differences," says Dr. Patricia Pelufo Silveira, lead author and associate professor in the Department of Psychiatry. "In the clinic, the presentation of depression is very different for men and women, as is their response to treatment, but we have very little understanding of why this happens at the moment."
Summary
There are marked sex differences in the prevalence, phenotypic presentation, and response to treatment for major depression. While genome-wide association studies (GWAS) adjust for sex differences, to date, no studies have sought to identify sex-specific markers and pathways.
In this study, we performed a sex-stratified genome-wide association analysis for broad depression with all UK Biobank participants (N = 274,141), including only unrelated participants, as well as men (N = 127,867). ) and women (N = 146,274) separately. Bioinformatic analyzes were performed to characterize common and sex-specific markers and associated processes/pathways.
We identified 11 loci passing significance at the genome level (P < 5 × 10−8) in women and one in men. In both men and women, genetic correlations were significant between GWA general depression and other psychopathologies; However, correlations with educational level and metabolic characteristics, including body fat, waist circumference, waist-to-hip ratio, and triglycerides , were significant only in women. Gene-based analysis showed 147 genes significantly associated with depression in the total sample, 64 in women and 53 in men.
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 (PRS) for general depression outperformed total and opposite-sex PRS in predicting 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.
In summary , our exploratory study suggests that the genetic background linked to human major depression includes sex-specific variants. There are common and unique biological mechanisms mapped from male-specific and female-specific MDD GWAS. Common processes such as regulation of gene expression and diseases such as brain pathology emerged from sex-specific gene networks. Our findings may contribute to the development of personalized therapeutic options. Consideration of sex-specific molecular alterations related to major depression during disease treatment may lead to a more effective response to antidepressants. Significantly larger samples in more diverse populations will be required to meet this goal. Our results are intended to contribute to the rationale for studies of sex-specific mechanisms. |
