| Title: | A sex-specific genome-wide association study of depression phenotypes in UK Biobank |
| Journal: | Molecular Psychiatry |
| Published: | 7 Feb 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36750733/ |
| DOI: | https://doi.org/10.1038/s41380-023-01960-0 |
| URL: | https://kclpure.kcl.ac.uk/portal/en/publications/b8c157ba-8393-446b-b59f-77b89d603b6d |
| Citations: | 25 (23 in last 2 years) as of 8 Aug 2024 |
Publication 11051
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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.</p>
11 Keywords
- Biological Specimen Banks
- Depression
- Depressive Disorder, Major
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Multifactorial Inheritance
- Phenotype
- United Kingdom
4 Authors
- Patrícia Pelufo Silveira
- Irina Pokhvisneva
- David M. Howard
- Michael J. Meaney
1 Application
| Application ID | Title |
|---|---|
| 41975 | Gene Network by environment (GnxE) study of impulsivity- methodology to extend GxE studies. |
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