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

TitleGenome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
Publication TypeJournal Article
Year of Publication2016
AuthorsHou L, Bergen SE, Akula N, Song J, Hultman CM, Landen M, Adli M, Alda M, Ardau R, Arias B et al.
JournalHum Mol Genet
Volume25
Issue15
Pagination3383-3394
Date Published2016 Aug 01
ISSN1460-2083
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.

DOI10.1093/hmg/ddw181
Alternate JournalHum. Mol. Genet.
PubMed ID27329760
PubMed Central IDPMC5179929
Grant ListR01 MH059556 / MH / NIMH NIH HHS / United States
R01 DA006227 / DA / NIDA NIH HHS / United States
R01 MH059535 / MH / NIMH NIH HHS / United States
R01 MH101782 / MH / NIMH NIH HHS / United States
R01 MH059567 / MH / NIMH NIH HHS / United States
R01 MH059545 / MH / NIMH NIH HHS / United States
R01 MH101810 / MH / NIMH NIH HHS / United States
R01 MH101819 / MH / NIMH NIH HHS / United States
P01 CA089392 / CA / NCI NIH HHS / United States
R01 DA033684 / DA / NIDA NIH HHS / United States
R01 MH090936 / MH / NIMH NIH HHS / United States
R01 MH059548 / MH / NIMH NIH HHS / United States
R01 MH059534 / MH / NIMH NIH HHS / United States
R01 MH059533 / MH / NIMH NIH HHS / United States
R01 MH090951 / MH / NIMH NIH HHS / United States
K02 DA021237 / DA / NIDA NIH HHS / United States
R01 MH101820 / MH / NIMH NIH HHS / United States
R01 MH101825 / MH / NIMH NIH HHS / United States
R01 MH090948 / MH / NIMH NIH HHS / United States
R01 MH090941 / MH / NIMH NIH HHS / United States
Z01 MH002810 / MH / NIMH NIH HHS / United States
R01 MH101822 / MH / NIMH NIH HHS / United States
HHSN261200800001C / RC / CCR NIH HHS / United States
R01 MH059553 / MH / NIMH NIH HHS / United States
R01 MH090937 / MH / NIMH NIH HHS / United States
HHSN268201000029C / HL / NHLBI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
R01 MH101814 / MH / NIMH NIH HHS / United States
R01 MH060068 / MH / NIMH NIH HHS / United States