October 9, 2025, 9:10 am | Read time: 6 minutes
It’s well-known that women are more likely to suffer from depression than men. A new study has now revealed that the genetic architecture of depression systematically differs between genders. According to the study, genetics plays a significantly larger role in the risk of depression for women. FITBOOK delves deeper into this topic.
Study on Genetic Causes of Depression Risk
Depression can manifest differently from person to person. There are also notable differences between genders in terms of prevalence and presentation. This is outlined in the introduction of the current study.1 Globally, women are almost twice as likely to be affected by this mental disorder compared to men. In women, depression often presents as atypical depression, characterized by weight gain and increased need for sleep. Additionally, women are more likely to suffer from immuno-metabolic depression, which involves inflammatory processes in the body that can disrupt metabolic regulation. In contrast, depression in men is often marked by anger, aggressive behavior, and tendencies toward drug and alcohol abuse.
Until now, it was assumed that external factors leading to psychological stress and hormonal influences were primarily responsible for the gender disparity. However, the different manifestations suggest that biological causes might also be significant. The study found that genetics indeed seems to explain a large part of the depression risk in women.
Details of the Study
The aim of the study was to better understand the genetic differences between women and men that play a role in depression risk. Researchers analyzed DNA data from more than half a million people with and without depression, including around 130,000 affected women and 65,000 affected men. The datasets came from international genome-wide association studies (GWAS), which are scientific studies examining genetic variations in the genome. Researchers also had information on whether the participants suffered from depression.
Researchers examined the data at millions of positions in the genome—separately for women and men. At each position, they checked whether certain variants were more common in people with depression than in those without. If so, they considered these variants as potentially associated with the disease. In the next step, they reviewed the results and information from other research projects and databases. Using a meta-analysis, they combined the results of all available datasets to increase the statistical power of their work.
Analyses of the Biological Significance of Genes for Depression
After identifying which specific genetic variants are associated with depression, researchers explored the biological significance of these findings. They aimed to understand to what extent the risk of developing depression is genetically determined and whether the same genes are active in both women and men. Where exactly are these relevant genes active: in the brain, the immune system, or the metabolism? To find out, they conducted bioinformatic analyses, linking their genetic data with databases that record which genes are active in which tissues and with which processes they are associated.
To determine whether the genes associated with depression also relate to other traits (such as body weight or the immune system), they conducted targeted statistical calculations on genetic correlations. They found that genetic patterns in women were more strongly linked to these physical processes than in men.
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Genes Have a Stronger Influence on Depression Risk in Women
According to the analysis, the genetic burden for depression is significantly higher in women than in men. This is evident in the involvement of more genetic variants (SNPs) in women. Estimates suggest there are around 13,244 causal variants in women, explaining 90 percent of the genetic variance. In men, there are comparatively fewer, with 7,111.
Researchers found that, in addition to genetic risk factors that affect both genders similarly, there are specific variants that play a role only or more strongly in women with depression. For better understanding: The genes that increase depression risk in men fall into the “Shared” category—meaning they are shared by both genders.
Another interesting aspect of the study is that in women, there is a stronger connection between genetic risk factors and physical traits like metabolic processes or body weight. This could explain why, as mentioned earlier, women with depression often gain weight and have an increased need for sleep. In women, the genes that predispose to depression are active very early in brain development—especially in regions responsible for emotions, memory, and partly movement. This might explain why depression in women sometimes progresses differently than in men.
In men, researchers discovered a previously unknown genetic variant on the X chromosome. According to the data, this is linked to depression risk. It belongs to a gene important for the function of the hippocampus—a brain region significant for memory and emotions.
Study Author Explains the Results for FITBOOK
The findings of the study could help in treating depression more effectively in the future. They show that the condition in women and men is partly based on different genetic foundations. Particularly noteworthy, as study author Dr. Jodi Thomas explains to FITBOOK, is a previously unknown genetic variant on the X chromosome identified only in men. This variant had not appeared in any previous depression study, not even in the largest GWAS to date with over a million participants. This underscores the importance of considering women and men separately in genetic research. For the future, Thomas sees great potential in integrating genetic insights more into clinical practice to better understand, diagnose, and treat depression.
However, there are also limitations. The software used could not account for all possible influencing factors, which may have affected the results due to various confounding factors. Additionally, the sample size for women was significantly larger than for men, which could exaggerate gender differences in the number of variants found. However, Thomas emphasizes that the quantity is less important than which variants were found. Furthermore, the genetic data were reviewed before the study, without specific controls for gender-specific differences. This could have led to technical distortions. Moreover, only participants of European descent were studied, so the results may not be directly applicable to other populations. Future research must therefore include other populations, Thomas notes. Nonetheless, the higher depression rate in women is observed worldwide and across cultures.