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

eQTLGen Consortium, BIOS Consortium, the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticle

11 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 (US)
Pages (from-to)793-803
Number of pages11
JournalNature genetics
Volume51
Issue number5
DOIs
StatePublished - May 1 2019

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Genome-Wide Association Study
Bipolar Disorder
Genome
Neurotransmitter Transport Proteins
Endocannabinoids
Genetic Heterogeneity
Major Depressive Disorder
Ion Channels
Psychotic Disorders
Genes
Psychiatry
Schizophrenia
Insulin

ASJC Scopus subject areas

  • Genetics

Cite this

eQTLGen Consortium, BIOS Consortium, & 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(5), 793-803. https://doi.org/10.1038/s41588-019-0397-8

Genome-wide association study identifies 30 loci associated with bipolar disorder. / eQTLGen Consortium; BIOS Consortium; the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium.

In: Nature genetics, Vol. 51, No. 5, 01.05.2019, p. 793-803.

Research output: Contribution to journalArticle

eQTLGen Consortium, BIOS Consortium & the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium 2019, 'Genome-wide association study identifies 30 loci associated with bipolar disorder', Nature genetics, vol. 51, no. 5, pp. 793-803. https://doi.org/10.1038/s41588-019-0397-8
eQTLGen Consortium, BIOS Consortium, the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. Genome-wide association study identifies 30 loci associated with bipolar disorder. Nature genetics. 2019 May 1;51(5):793-803. https://doi.org/10.1038/s41588-019-0397-8
eQTLGen Consortium ; BIOS Consortium ; the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. / Genome-wide association study identifies 30 loci associated with bipolar disorder. In: Nature genetics. 2019 ; Vol. 51, No. 5. pp. 793-803.
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