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

TY - JOUR

T1 - Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression

AU - Guintivano, Jerry

AU - Byrne, Enda M

AU - Kiewa, Jacqueline

AU - Yao, Shuyang

AU - Bauer, Anna E

AU - Aberg, Karolina A

AU - Adams, Mark J

AU - Campbell, Archie

AU - Campbell, Megan L

AU - Choi, Karmel W

AU - Corfield, Elizabeth C

AU - Havdahl, Alexandra

AU - Hucks, Donald

AU - Koen, Nastassja

AU - Lu, Yi

AU - Mægbæk, Merete L

AU - Mullaert, Jimmy

AU - Peterson, Roseann E

AU - Raffield, Laura M

AU - Sallis, Hannah M

AU - Sealock, Julia M

AU - Walker, Alicia

AU - Watson, Hunna J

AU - Xiong, Ying

AU - Yang, Jessica M K

AU - Anney, Richard J L

AU - Gordon-Smith, Katherine

AU - Hubbard, Leon

AU - Jones, Lisa A

AU - Mihaescu, Raluca

AU - Nyegaard, Mette

AU - Pardiñas, Antonio F

AU - Perry, Amy

AU - Saquib, Nazmus

AU - Shadyab, Aladdin H

AU - Viktorin, Alexander

AU - Andreassen, Ole A

AU - Bigdeli, Tim B

AU - Davis, Lea K

AU - Dennis, Cindy-Lee

AU - Di Florio, Arianna

AU - Dubertret, Caroline

AU - Feng, Yen-Chen A

AU - Frey, Benicio N

AU - Grigoriadis, Sophie

AU - Gloaguen, Emilie

AU - Jones, Ian

AU - Munk-Olsen, Trine

AU - Stein, Dan J

AU - Wray, Naomi

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2023/12/1

Y1 - 2023/12/1

N2 - OBJECTIVE: 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.METHOD: 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.RESULTS: 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.CONCLUSIONS: 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).

AB - OBJECTIVE: 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.METHOD: 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.RESULTS: 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.CONCLUSIONS: 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).

KW - Female

KW - Humans

KW - Animals

KW - Mice

KW - Depressive Disorder, Major/genetics

KW - Genome-Wide Association Study

KW - Depression, Postpartum/genetics

KW - Genetic Predisposition to Disease

KW - Bipolar Disorder/genetics

KW - Polymorphism, Single Nucleotide/genetics

U2 - 10.1176/appi.ajp.20230053

DO - 10.1176/appi.ajp.20230053

M3 - Journal article

C2 - 37849304

SN - 1139-3475

VL - 180

SP - 884

EP - 895

JO - The American Journal of Psychiatry (Spanish Edition)

JF - The American Journal of Psychiatry (Spanish Edition)

IS - 12

ER -