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<p>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>

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Sex-stratified genome-wide association meta-analysis of major depressive disorder

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月26日

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  • Jodi T. Thomas,
  • Jackson G. Thorp,
  • Floris Huider,
  • Poppy Z. Grimes,
  • Rujia Wang,
  • Pierre Youssef,
  • Jonathan R. I. Coleman,
  • Enda M. Byrne,
  • Mark Adams,
  • Hanna M. van Loo,
  • Brenda W. J. H. Penninx,
  • 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

摘要

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.