Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
Title | Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Hou L, Bergen SE, Akula N, Song J, Hultman CM, Landen M, Adli M, Alda M, Ardau R, Arias B et al. |
Journal | Hum Mol Genet |
Volume | 25 |
Issue | 15 |
Pagination | 3383-3394 |
Date Published | 2016 Aug 01 |
ISSN | 1460-2083 |
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. |
DOI | 10.1093/hmg/ddw181 |
Alternate Journal | Hum. Mol. Genet. |
PubMed ID | 27329760 |
PubMed Central ID | PMC5179929 |
Grant List | R01 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 |