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

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Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression. / Guintivano, Jerry; Byrne, Enda M.; Kiewa, Jacqueline; Yao, Shuyang; Bauer, Anna E.; Aberg, Karolina A.; Adams, Mark J.; Campbell, Archie; Campbell, Megan L.; Choi, Karmel W.; Corfield, Elizabeth C.; Havdahl, Alexandra; Hucks, Donald; Koen, Nastassja; Lu, Yi; Mægbæk, Merete L.; Mullaert, Jimmy; Peterson, Roseann E.; Raffield, Laura M.; Sallis, Hannah M.; Sealock, Julia M.; Walker, Alicia; Watson, Hunna J.; Xiong, Ying; Yang, Jessica M. K.; Anney, Richard J. L.; Gordon-Smith, Katherine; Hubbard, Leon; Jones, Lisa A.; Mihaescu, Raluca; Nyegaard, Mette; Pardiñas, Antonio F.; Perry, Amy; Saquib, Nazmus; Shadyab, Aladdin H.; Viktorin, Alexander; Andreassen, Ole A.; Bigdeli, Tim B.; Davis, Lea K.; Dennis, Cindy-Lee; Di Florio, Arianna; Dubertret, Caroline; Feng, Yen-Chen A.; Frey, Benicio N.; Grigoriadis, Sophie; Gloaguen, Emilie; Jones, Ian; Kennedy, James L.; Krohn, Holly; Kallak, Theodora Kunovac; Li, Yun; Martin, Nicholas G.; McIntosh, Andrew M.; Milgrom, Jeannette; Munk-Olsen, Trine; Oberlander, Tim; Olsen, Catherine M.; Ramoz, Nicolas; Reichborn-Kjennerud, Ted; Blackmore, Emma Robertson; Rubinow, David; Skalkidou, Alkistis; Smoller, Jordan W.; Stein, Dan J.; Stowe, Zachary N.; Taylor, Valerie; Tebeka, Sarah; Tesli, Martin; Van Lieshout, Ryan J.; van den Oord, Edwin J. C. G.; Vigod, Simone N.; Werge, Thomas; Westlye, Lars T.; Whiteman, David C.; Zar, Heather J.; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Wray, Naomi; Meltzer-Brody, Samantha; Sullivan, Patrick.

In: The American Journal of Psychiatry, Vol. 180, No. 12, 2023, p. 884-895.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Guintivano, J, Byrne, EM, Kiewa, J, Yao, S, Bauer, AE, Aberg, KA, Adams, MJ, Campbell, A, Campbell, ML, Choi, KW, Corfield, EC, Havdahl, A, Hucks, D, Koen, N, Lu, Y, Mægbæk, ML, Mullaert, J, Peterson, RE, Raffield, LM, Sallis, HM, Sealock, JM, Walker, A, Watson, HJ, Xiong, Y, Yang, JMK, Anney, RJL, Gordon-Smith, K, Hubbard, L, Jones, LA, Mihaescu, R, Nyegaard, M, Pardiñas, AF, Perry, A, Saquib, N, Shadyab, AH, Viktorin, A, Andreassen, OA, Bigdeli, TB, Davis, LK, Dennis, C-L, Di Florio, A, Dubertret, C, Feng, Y-CA, Frey, BN, Grigoriadis, S, Gloaguen, E, Jones, I, Kennedy, JL, Krohn, H, Kallak, TK, Li, Y, Martin, NG, McIntosh, AM, Milgrom, J, Munk-Olsen, T, Oberlander, T, Olsen, CM, Ramoz, N, Reichborn-Kjennerud, T, Blackmore, ER, Rubinow, D, Skalkidou, A, Smoller, JW, Stein, DJ, Stowe, ZN, Taylor, V, Tebeka, S, Tesli, M, Van Lieshout, RJ, van den Oord, EJCG, Vigod, SN, Werge, T, Westlye, LT, Whiteman, DC, Zar, HJ, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Wray, N, Meltzer-Brody, S & Sullivan, P 2023, 'Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression', The American Journal of Psychiatry, vol. 180, no. 12, pp. 884-895. https://doi.org/10.1176/appi.ajp.20230053

APA

Guintivano, J., Byrne, E. M., Kiewa, J., Yao, S., Bauer, A. E., Aberg, K. A., Adams, M. J., Campbell, A., Campbell, M. L., Choi, K. W., Corfield, E. C., Havdahl, A., Hucks, D., Koen, N., Lu, Y., Mægbæk, M. L., Mullaert, J., Peterson, R. E., Raffield, L. M., ... Sullivan, P. (2023). Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression. The American Journal of Psychiatry, 180(12), 884-895. https://doi.org/10.1176/appi.ajp.20230053

Vancouver

Guintivano J, Byrne EM, Kiewa J, Yao S, Bauer AE, Aberg KA et al. Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression. The American Journal of Psychiatry. 2023;180(12):884-895. https://doi.org/10.1176/appi.ajp.20230053

Author

Guintivano, Jerry ; Byrne, Enda M. ; Kiewa, Jacqueline ; Yao, Shuyang ; Bauer, Anna E. ; Aberg, Karolina A. ; Adams, Mark J. ; Campbell, Archie ; Campbell, Megan L. ; Choi, Karmel W. ; Corfield, Elizabeth C. ; Havdahl, Alexandra ; Hucks, Donald ; Koen, Nastassja ; Lu, Yi ; Mægbæk, Merete L. ; Mullaert, Jimmy ; Peterson, Roseann E. ; Raffield, Laura M. ; Sallis, Hannah M. ; Sealock, Julia M. ; Walker, Alicia ; Watson, Hunna J. ; Xiong, Ying ; Yang, Jessica M. K. ; Anney, Richard J. L. ; Gordon-Smith, Katherine ; Hubbard, Leon ; Jones, Lisa A. ; Mihaescu, Raluca ; Nyegaard, Mette ; Pardiñas, Antonio F. ; Perry, Amy ; Saquib, Nazmus ; Shadyab, Aladdin H. ; Viktorin, Alexander ; Andreassen, Ole A. ; Bigdeli, Tim B. ; Davis, Lea K. ; Dennis, Cindy-Lee ; Di Florio, Arianna ; Dubertret, Caroline ; Feng, Yen-Chen A. ; Frey, Benicio N. ; Grigoriadis, Sophie ; Gloaguen, Emilie ; Jones, Ian ; Kennedy, James L. ; Krohn, Holly ; Kallak, Theodora Kunovac ; Li, Yun ; Martin, Nicholas G. ; McIntosh, Andrew M. ; Milgrom, Jeannette ; Munk-Olsen, Trine ; Oberlander, Tim ; Olsen, Catherine M. ; Ramoz, Nicolas ; Reichborn-Kjennerud, Ted ; Blackmore, Emma Robertson ; Rubinow, David ; Skalkidou, Alkistis ; Smoller, Jordan W. ; Stein, Dan J. ; Stowe, Zachary N. ; Taylor, Valerie ; Tebeka, Sarah ; Tesli, Martin ; Van Lieshout, Ryan J. ; van den Oord, Edwin J. C. G. ; Vigod, Simone N. ; Werge, Thomas ; Westlye, Lars T. ; Whiteman, David C. ; Zar, Heather J. ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ; Wray, Naomi ; Meltzer-Brody, Samantha ; Sullivan, Patrick. / Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression. In: The American Journal of Psychiatry. 2023 ; Vol. 180, No. 12. pp. 884-895.

Bibtex

@article{46a62932510148f9b5098561167bca5a,
title = "Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression",
abstract = "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).",
keywords = "Female, Humans, Animals, Mice, Depressive Disorder, Major/genetics, Genome-Wide Association Study, Depression, Postpartum/genetics, Genetic Predisposition to Disease, Bipolar Disorder/genetics, Polymorphism, Single Nucleotide/genetics",
author = "Jerry Guintivano and Byrne, {Enda M.} and Jacqueline Kiewa and Shuyang Yao and Bauer, {Anna E.} and Aberg, {Karolina A.} and Adams, {Mark J.} and Archie Campbell and Campbell, {Megan L.} and Choi, {Karmel W.} and Corfield, {Elizabeth C.} and Alexandra Havdahl and Donald Hucks and Nastassja Koen and Yi Lu and M{\ae}gb{\ae}k, {Merete L.} and Jimmy Mullaert and Peterson, {Roseann E.} and Raffield, {Laura M.} and Sallis, {Hannah M.} and Sealock, {Julia M.} and Alicia Walker and Watson, {Hunna J.} and Ying Xiong and Yang, {Jessica M. K.} and Anney, {Richard J. L.} and Katherine Gordon-Smith and Leon Hubbard and Jones, {Lisa A.} and Raluca Mihaescu and Mette Nyegaard and Pardi{\~n}as, {Antonio F.} and Amy Perry and Nazmus Saquib and Shadyab, {Aladdin H.} and Alexander Viktorin and Andreassen, {Ole A.} and Bigdeli, {Tim B.} and Davis, {Lea K.} and Cindy-Lee Dennis and {Di Florio}, Arianna and Caroline Dubertret and Feng, {Yen-Chen A.} and Frey, {Benicio N.} and Sophie Grigoriadis and Emilie Gloaguen and Ian Jones and Kennedy, {James L.} and Holly Krohn and Kallak, {Theodora Kunovac} and Yun Li and Martin, {Nicholas G.} and McIntosh, {Andrew M.} and Jeannette Milgrom and Trine Munk-Olsen and Tim Oberlander and Olsen, {Catherine M.} and Nicolas Ramoz and Ted Reichborn-Kjennerud and Blackmore, {Emma Robertson} and David Rubinow and Alkistis Skalkidou and Smoller, {Jordan W.} and Stein, {Dan J.} and Stowe, {Zachary N.} and Valerie Taylor and Sarah Tebeka and Martin Tesli and {Van Lieshout}, {Ryan J.} and {van den Oord}, {Edwin J. C. G.} and Vigod, {Simone N.} and Thomas Werge and Westlye, {Lars T.} and Whiteman, {David C.} and Zar, {Heather J.} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Naomi Wray and Samantha Meltzer-Brody and Patrick Sullivan",
year = "2023",
doi = "10.1176/appi.ajp.20230053",
language = "English",
volume = "180",
pages = "884--895",
journal = "The American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Publishing, Inc.",
number = "12",

}

RIS

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 - Kennedy, James L.

AU - Krohn, Holly

AU - Kallak, Theodora Kunovac

AU - Li, Yun

AU - Martin, Nicholas G.

AU - McIntosh, Andrew M.

AU - Milgrom, Jeannette

AU - Munk-Olsen, Trine

AU - Oberlander, Tim

AU - Olsen, Catherine M.

AU - Ramoz, Nicolas

AU - Reichborn-Kjennerud, Ted

AU - Blackmore, Emma Robertson

AU - Rubinow, David

AU - Skalkidou, Alkistis

AU - Smoller, Jordan W.

AU - Stein, Dan J.

AU - Stowe, Zachary N.

AU - Taylor, Valerie

AU - Tebeka, Sarah

AU - Tesli, Martin

AU - Van Lieshout, Ryan J.

AU - van den Oord, Edwin J. C. G.

AU - Vigod, Simone N.

AU - Werge, Thomas

AU - Westlye, Lars T.

AU - Whiteman, David C.

AU - Zar, Heather J.

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

AU - Wray, Naomi

AU - Meltzer-Brody, Samantha

AU - Sullivan, Patrick

PY - 2023

Y1 - 2023

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

VL - 180

SP - 884

EP - 895

JO - The American Journal of Psychiatry

JF - The American Journal of Psychiatry

SN - 0002-953X

IS - 12

ER -

ID: 385221849