| Title: | Sex-stratified genome-wide association meta-analysis of major depressive disorder |
| Journal: | Nature Communications |
| Published: | 26 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40858613/ |
| DOI: | https://doi.org/10.1038/s41467-025-63236-1 |
| URL: | https://www.nature.com/articles/s41467-025-63236-1.pdf |
Publication 19655
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Abstract
There are striking sex differences in the prevalence and symptomology of Major Depressive Disorder. Here, we conduct the largest sex-stratified genome wide association and genotype-by-sex interaction meta-analyses of Major Depressive Disorder to date (Females: 130,471 cases, 159,521 controls. Males: 64,805 cases, 132,185 controls). We identify 16 and eight independent genome-wide significant variants in females and males, respectively, including one novel variant on the X chromosome. Major Depressive Disorder in females and males shows substantial genetic overlap with a large proportion of variants displaying similar effect sizes across sexes. However, we also provide evidence for a higher burden of genetic risk in females which could be due to female-specific variants. Additionally, sex-specific pleiotropic effects may contribute to the higher prevalence of metabolic symptoms in females with Major Depressive Disorder. These findings underscore the importance of considering sex-specific genetic architectures in the study of health conditions, including Major Depressive Disorder, paving the way for more targeted treatment strategies.</p>
9 Keywords
- Depressive Disorder, Major
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Genotype
- Humans
- Male
- Polymorphism, Single Nucleotide
- Sex Factors
23 Authors
- Jodi T. Thomas
- Jackson G. Thorp
- Floris Huider
- Poppy Z. Grimes
- Rujia Wang
- Pierre Youssef
- Jonathan R. I. Coleman
- Enda M. Byrne
- Mark Adams
- Sarah E. Medland
- Ian B. Hickie
- Catherine M. Olsen
- David C. Whiteman
- Heather C. Whalley
- Brenda W.J.H. Penninx
- Hanna M. van Loo
- Eske M. Derks
- Thalia C. Eley
- Gerome Breen
- Dorret I. Boomsma
- Naomi R. Wray
- Nicholas G. Martin
- Brittany L. Mitchell
1 Application
| Application ID | Title |
|---|---|
| 25331 | Gene mapping and genetic correlation across complex traits |
Enabling scientific discoveries that improve human health