Sex Differences in the Genetics of Depression

Repository for scripts used for sex-stratified GWAS and genome-wide genotype-by-sex interaction meta-analyses of Major Depressive Disorder, and downstream analyses

This repository has been archived on Zenodo and assigned a DOI:

The associated publication for this repository:

Thomas, J.T., Thorp, J.G., Huider, F. et al. Sex-stratified genome-wide association meta-analysis of major depressive disorder. Nature Communications 16, 7960 (2025).

The summary statistics are available on GWAS Catalog:

: Female GWAS
: Male GWAS
: genotype-by-sex interaction (X chromosome with full dosage compensation) : genotype-by-sex interaction (X chromosome with no dosage compensation)

Cohorts

• The Australian Genetics of Depression Study (AGDS) in Australia
  • Female: cases=10,406, controls=7,147
  • Male: cases=3,174, controls=6,601)
• The BIObanks Netherlands Internet Collaboration (BIONIC) in the Netherlands
  • Female: cases=10,664 , controls=26,878
  • Male: cases=4,432, controls=20,013)
• Genetic Links to Anxiety and Depression (GLAD+) study in the United Kingdom (UK)
  • Female: cases=16,708 , controls=3,393
  • Male: cases=4,656, controls=3,025)
• UK Biobank from the UK
  • Female: cases=46,194, controls=53,211
  • Male: cases=22,608, controls=56,516
• All Of Us from the United States of America
  • Female: cases=26,776, controls=46,678
  • Male: cases=11,136, controls=35,836).
• Blokland et al., 2022 meta-analysis including Psychiatric Genomics Consortium (PGC) cohorts and iPSYCH
  • Blokland GAM, et al., Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. Biol Psychiatry, 2022. 91(1):102-117.
  • Female: cases=19,723, controls=22,214
  • Male: cases=18,799, controls=10,194

TOTAL sample size = 130,471 cases and 159,521 controls in females, and 64,805 cases and 132,185 controls in males

Analysts

• The analysis protocol was created by Jodi Thomas and the sex-stratified GWAS and genome-wide genotype-by-sex interaction analyses were carried out in each of the cohorts as follows
  • AGDS = Jodi Thomas
  • All Of Us = Jackson Thorp and Pierre Youssef
  • BIONIC = Floris Huider
  • GLAD+ = Rujia Wang
  • Generation Scotland = Popppy Grimes
  • UK Biobank = Jodi Thomas
• Jodi Thomas performed the meta-analyses and most of the downstream statistical and bioinformatics analyses, with MiXeR analyses being carried out by Jackson Thorp.