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

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.

SUBMITTER: Hou L 

PROVIDER: S-EPMC5179929 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature