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

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.

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Affiliated Institutions

• VIB-UAntwerp Center for Molecular Neurology BE
• Mario Negri Institute for Pharmacological Research IT
• University of California, Los Angeles US
• University Hospital Heidelberg DE
• University Hospital of Basel CH
• Johns Hopkins Medicine US
• University of Plymouth GB
• King's College London GB
• Translational Genomics Research Institute US
• University College London GB
• Medical Research Council GB
• Indiana University – Purdue University Indianapolis US
• Vall d'Hebron Hospital Universitari ES
• University of Bonn DE
• Charité - Universitätsmedizin Berlin DE
• University of Iowa Hospitals and Clinics US
• Poznan University of Medical Sciences PL
• Broad Institute US
• University of Oslo
• Icahn School of Medicine at Mount Sinai US
• Technische Universität Dresden DE
• University of Minnesota System US
• Ludwig-Maximilians-Universität München DE
• Karolinska Institutet SE
• UNSW Sydney AU
• University of Edinburgh GB
• Massachusetts General Hospital US
• University of California, Irvine US
• deCODE Genetics (Iceland) IS
• The University of Queensland AU
• University of Antwerp BE
• Rush University Medical Center US
• Lundbeck Foundation DK
• QIMR Berghofer Medical Research Institute AU
• University Hospital Bonn DE
• Amsterdam Neuroscience NL
• Dalhousie University CA
• University Medical Center Utrecht NL
• Vrije Universiteit Amsterdam NL
• University of Basel CH
• Cornell University US
• Philipps University of Marburg DE
• Cardiff University GB
• University of Tübingen DE
• Central Institute of Mental Health DE
• Universitätsklinikum Würzburg DE
• Aarhus University DK
• Diakonhjemmet Hospital
• Sankt Hans Hospital DK
• McGill University Health Centre CA
• Centro de Investigación Biomédica en Red de Salud Mental ES
• Oslo University Hospital
• University of Chicago US
• Berkshire Healthcare NHS Foundation Trust GB
• Statens Serum Institut DK
• Karolinska University Hospital SE
• Instituto de Investigación Biomédica de Málaga ES
• Inserm FR
• University Hospital Carl Gustav Carus DE
• University of Worcester GB
• Universitat Autònoma de Barcelona ES
• Queen Mary University of London GB
• University of California, San Diego US
• University of Michigan US
• Instituto de Salud Carlos III ES
• Howard University Hospital US
• Johns Hopkins University US
• University of Bergen
• University of California, San Francisco US
• Statistical Research (United States) US
• Heidelberg University DE
• Neuroscience Research Australia AU

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