Metabolic disorder and genetic differences associated with depression in women

Resume: Researchers identified 11 DNA regions linked to depression in women and one in men. They also found that depression is associated with metabolic disorders in women, which is an important new aspect to consider when treating depressive symptoms.

Source: McGill University

It is widely reported that depression is more common in women than men, with women being twice as likely to receive a diagnosis as men.

A new gender-specific study from McGill University has shown that there are differences between male and female genes and how they are related to depression.

In a study of more than 270,000 individuals, the researchers found that sex-specific prediction methods were more accurate at predicting a person’s genetic risk of developing depression than prediction methods that did not specify gender.

The researchers found 11 DNA regions associated with depression in women, and only one region in men. They also found that depression is specifically linked to metabolic disorders in women, an important aspect to consider when treating women with depression.

Despite the biological processes involved in depression being similar in men and women, researchers found that different genes were involved for each sex. This information may be helpful in identifying future sex-specific treatments for depression.

This shows the outline of a man and a woman's head
The researchers found 11 DNA regions associated with depression in women, and only one region in men. The image is in the public domain

“This is the first study to describe sex-specific genetic variants associated with depression, a common illness in both men and women. These findings are important for the development of specific therapies that will benefit both men and women while taking into account their differences,” said 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 understand very little why this is happening at this point.”

About this news about genetics and depression research

Author: Press Office
Source: McGill University
Contact: Press Service – McGill University
Image: The image is in the public domain

Original research: Open access.
“A sex-specific genome-wide association study of depression phenotypes in UK Biobank” by Patrícia Pelufo Silveira et al. Molecular Psychiatry


A sex-specific genome-wide association study of depression phenotypes in UK Biobank

There are clear sex differences in the prevalence, phenotypic presentation and treatment response for major depression. Although genome-wide association studies (GWAS) correct for sex differences, to date there have been no studies attempting to identify sex-specific markers and pathways.

In this study, we performed a sex-stratified genome-wide association analysis for broad depression with the total participants from the UK Biobank (N= 274,141), including unrelated participants only, as well as with men (N= 127,867) and females (N= 146,274) individually.

Bioinformatics analyzes were performed to characterize common and genus-specific markers and associated processes/pathways.

We identified 11 loci that passed on genome-level significance (P< 5 × 10−8) in females and one in males. In both men and women, there were significant genetic correlations between the broad depression GWA and other psychopathologies; however, correlations with education level and metabolic characteristics, including body fat, waist circumference, waist-to-hip ratio, and triglycerides, were only significant in women.

Gene-based analysis revealed 147 genes significantly associated with broad depression in the total sample, 64 in the women and 53 in the men.

Gene-based analysis revealed “regulation of gene expression” as a general biological process, but suggested sex-specific molecular mechanisms.

Finally, sex-specific polygenic risk scores (PRSs) for major depressive disorder outperformed total PRSs and PRSs of the opposite sex in predicting major depressive disorder.

These findings provide evidence for sex-dependent genetic pathways for clinical depression and for health problems comorbid with depression.

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