Abstract summary 

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

Authors & Co-authors:  Guintivano Jerry J Byrne Enda M EM Kiewa Jacqueline J Yao Shuyang S Bauer Anna E AE Aberg Karolina A KA Adams Mark J MJ Campbell Archie A Campbell Megan L ML Choi Karmel W KW Corfield Elizabeth C EC Havdahl Alexandra A Hucks Donald D Koen Nastassja N Lu Yi Y Mægbæk Merete L ML Mullaert Jimmy J Peterson Roseann E RE Raffield Laura M LM Sallis Hannah M HM Sealock Julia M JM Walker Alicia A Watson Hunna J HJ Xiong Ying Y Yang Jessica M K JMK Anney Richard J L RJL Gordon-Smith Katherine K Hubbard Leon L Jones Lisa A LA Mihaescu Raluca R Nyegaard Mette M Pardiñas Antonio F AF Perry Amy A Saquib Nazmus N Shadyab Aladdin H AH Viktorin Alexander A Andreassen Ole A OA Bigdeli Tim B TB Davis Lea K LK Dennis Cindy-Lee CL Di Florio Arianna A Dubertret Caroline C Feng Yen-Chen A YA Frey Benicio N BN Grigoriadis Sophie S Gloaguen Emilie E Jones Ian I Kennedy James L JL Krohn Holly H Kunovac Kallak Theodora T Li Yun Y Martin Nicholas G NG McIntosh Andrew M AM Milgrom Jeannette J Munk-Olsen Trine T Oberlander Tim T Olsen Catherine M CM Ramoz Nicolas N Reichborn-Kjennerud Ted T Robertson Blackmore Emma E Rubinow David D Skalkidou Alkistis A Smoller Jordan W JW Stein Dan J DJ Stowe Zachary N ZN Taylor Valerie V Tebeka Sarah S Tesli Martin M Van Lieshout Ryan J RJ van den Oord Edwin J C G EJCG Vigod Simone N SN Werge Thomas T Westlye Lars T LT Whiteman David C DC Zar Heather J HJ Wray Naomi N Meltzer-Brody Samantha S Sullivan Patrick P

Study Outcome 

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