Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression

• DOI: 10.1176/appi.ajp.20230053
• Publication Date: 2023-10-18T07:01:25Z
• Authors: Jerry Guintivano; Enda M. Byrne; Jacqueline Kiewa; Shuyang Yao; Anna E. Bauer; Karolina A. Aberg; Mark J. Adams; Archie Campbell; Megan L. Campbell; Karmel W. Choi; Elizabeth C. Corf...; Alexandra Havdahl; Donald Hucks; Nastassja Koen; Yi Lu; Merete L. Mægbæk; Jimmy Mullaert; Roseann E. Peterson; Laura M. Raffield; Hannah M. Sallis; Julia M. Sealock; Alicia Walker; Hunna J. Watson; Ying Xiong; Jessica M.K. Yang; Richard J.L. Anney; Katherine Gordon-...; Leon Hubbard; Lisa A. Jones; Raluca Mihaescu; Mette Nyegaard; Antonio F. Pardiñas; Amy Perry; Nazmus Saquib; Aladdin H. Shadyab; Alexander Viktorin; Ole A. Andreassen; Tim B. Bigdeli; Lea K. Davis; Cindy-Lee Dennis; Arianna Di Florio; Caroline Dubertret; Yen-Chen A. Feng; Benicio N. Frey; Sophie Grigoriadis; Emilie Gloaguen; Ian Jones; James L. Kennedy; Holly Krohn; Theodora Kunovac ...; Yun Li; Nicholas G. Martin; Andrew M. McIntosh; Jeannette Milgrom; Trine Munk-Olsen; Tim Oberlander; Catherine M. Olsen; Nicolas Ramoz; Ted Reichborn-Kje...; Emma Robertson Bl...; David Rubinow; Alkistis Skalkidou; Jordan W. Smoller; Dan J. Stein; Zachary N. Stowe; Valerie Taylor; Sarah Tebeka; Martin Tesli; Ryan J. Van Lieshout; Edwin J.C.G. van ...; Simone N. Vigod; Thomas Werge; Lars T. Westlye; David C. Whiteman; Heather J. Zar; ; Naomi Wray; Samantha Meltzer-...; Patrick Sullivan
• Keywords: Depression; Genome-wide Association Study; Association (psychology); Genetic Association

Objective: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that more heritable, yet understudied in psychiatric genetics. The authors conducted meta-analyses genome-wide association studies (GWASs) to investigate the genetic architecture PPD. Method: Meta-analyses were on 18 cohorts European ancestry (17,339 PPD cases and 53,426 controls), one cohort East Asian (975 3,780 African (456 1,255 totaling 18,770 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)–based heritability , 2) correlations between other phenotypes, 3) enrichment GWAS findings 27 human tissues 265 cell types from mouse central peripheral nervous system. Results: No SNP achieved significance or trans-ancestry meta-analyses. was 0.14 (SE=0.02). Significant estimated for with MDD, bipolar disorder, anxiety disorders, posttraumatic stress insomnia, age at menarche, polycystic ovary syndrome. Cell-type implicate inhibitory neurons thalamus cholinergic within septal nuclei hypothalamus, pattern differs MDD. Conclusions: While samples are needed reach levels significance, results presented confirm as polygenic heritable phenotype. There also evidence despite high correlation may have unique components. Cell suggest GABAergic neurons, which converge mechanism only medication approved by U.S. Food Drug Administration (brexanolone).