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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

Journal article published in 2016 by Liping Hou, Sarah E. Bergen, Nirmala Akula, Christina M. Hultman, Jie Song, Jean-Michel Aubry, Judith A. Badner, Thomas B. Barrett, Mikael Landen, Bergen Se, Bernhard T. Baune, Mazda Adli, Wade H. Berrettini, Abesh Kumar Bhattacharjee, Martin Alda and other authors.
This paper is available in a repository.
This paper is available in a repository.

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Abstract

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 × 10 (-) (9); odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 × 10 (-) (9); OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.