Genome-wide association study identifies five new schizophrenia loci.

TitleGenome-wide association study identifies five new schizophrenia loci.
Publication TypeJournal Article
Year of Publication2011
Corporate AuthorsSchizophrenia Psychiatric Genome-Wide Association Study(GWAS) Consortium
JournalNat Genet
Volume43
Issue10
Pagination969-76
Date Published2011 Sep 18
ISSN1546-1718
KeywordsAlleles, Bipolar Disorder, Case-Control Studies, Female, Gene Dosage, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Haplotypes, Humans, Linkage Disequilibrium, Logistic Models, Male, MicroRNAs, Mutation, Polymorphism, Single Nucleotide, Schizophrenia, Whites
Abstract

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

DOI10.1038/ng.940
Alternate JournalNat Genet
Original PublicationGenome-wide association study identifies five new schizophrenia loci.
PubMed ID21926974
PubMed Central IDPMC3303194
Grant ListU01 MH085515 / MH / NIMH NIH HHS / United States
R01 MH078075 / MH / NIMH NIH HHS / United States
K01 MH085812 / MH / NIMH NIH HHS / United States
P30 MH074543 / MH / NIMH NIH HHS / United States
R01 MH071681 / MH / NIMH NIH HHS / United States
G1000708 / MRC_ / Medical Research Council / United Kingdom
G0800509 / MRC_ / Medical Research Council / United Kingdom
R01 MH067257 / MH / NIMH NIH HHS / United States
R01 MH059587 / MH / NIMH NIH HHS / United States
R01 MH059586 / MH / NIMH NIH HHS / United States
R01 MH080403 / MH / NIMH NIH HHS / United States
R01 MH068921 / MH / NIMH NIH HHS / United States
P50 MH066392 / MH / NIMH NIH HHS / United States
R37 GM047845-21 / GM / NIGMS NIH HHS / United States
R01 MH060879 / MH / NIMH NIH HHS / United States
R01 MH074027 / MH / NIMH NIH HHS / United States
R01 MH061675 / MH / NIMH NIH HHS / United States
K23 MH001760 / MH / NIMH NIH HHS / United States
U01 MH085518 / MH / NIMH NIH HHS / United States
U01 MH085520 / MH / NIMH NIH HHS / United States
R01 MH079800 / MH / NIMH NIH HHS / United States
R01 MH061884 / MH / NIMH NIH HHS / United States
R01 MH058693 / MH / NIMH NIH HHS / United States
R01 CA082659-12 / CA / NCI NIH HHS / United States
R01 MH084098 / MH / NIMH NIH HHS / United States
R01 MH077139 / MH / NIMH NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01 MH068881 / MH / NIMH NIH HHS / United States
R01 MH060870 / MH / NIMH NIH HHS / United States
R01 MH062276 / MH / NIMH NIH HHS / United States
G1000718 / MRC_ / Medical Research Council / United Kingdom
U01 MH079470 / MH / NIMH NIH HHS / United States
090532 / / Wellcome Trust / United Kingdom
R01 MH085548 / MH / NIMH NIH HHS / United States
R01 MH059566 / MH / NIMH NIH HHS / United States
R01 MH083094 / MH / NIMH NIH HHS / United States
U01 MH094421 / MH / NIMH NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
R01 MH059588 / MH / NIMH NIH HHS / United States
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