Genome-wide association study identifies 30 loci associated with bipolar disorder

Eli A. Stahl* (Corresponding Author), Gerome Breen, Andreas J. Forstner, Andrew McQuillin, Stephan Ripke, Vassily Trubetskoy, Manuel Mattheisen, Yunpeng Wang, Jonathan R.I. Coleman, Héléna A. Gaspar, Christiaan A. de Leeuw, Stacy Steinberg, Jennifer M.Whitehead Pavlides, Maciej Trzaskowski, Enda M. Byrne, Tune H. Pers, Peter A. Holmans, Alexander L. Richards, Liam Abbott, Esben AgerboHuda Akil, Diego Albani, Ney Alliey-Rodriguez, Thomas D. Als, Adebayo Anjorin, Verneri Antilla, Swapnil Awasthi, Judith A. Badner, Marie Bækvad-Hansen, Jack D. Barchas, Nicholas Bass, Michael Bauer, Richard Belliveau, Sarah E. Bergen, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, James Boocock, Monika Budde, William Bunney, Margit Burmeister, Jonas Bybjerg-Grauholm, William Byerley, Miquel Casas, Felecia Cerrato, Pablo Cervantes, Kimberly Chambert, Alexander W. Charney, Danfeng Chen, David St Clair, eQTLGen Consortium, BIOS Consortium, the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

*Corresponding author for this work

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10 −4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10 −8 ) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

Original languageEnglish
Pages (from-to)793-803
Number of pages11
JournalNature Genetics
Volume51
DOIs
Publication statusPublished - 1 May 2019

Keywords

  • Bipolar disorder
  • genomes

ASJC Scopus subject areas

  • Genetics

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    Stahl, E. A., Breen, G., Forstner, A. J., McQuillin, A., Ripke, S., Trubetskoy, V., Mattheisen, M., Wang, Y., Coleman, J. R. I., Gaspar, H. A., de Leeuw, C. A., Steinberg, S., Pavlides, J. M. W., Trzaskowski, M., Byrne, E. M., Pers, T. H., Holmans, P. A., Richards, A. L., Abbott, L., ... the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium (2019). Genome-wide association study identifies 30 loci associated with bipolar disorder. Nature Genetics, 51, 793-803. https://doi.org/10.1038/s41588-019-0397-8