BACKGROUND: We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia. METHODS: The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis. RESULTS: One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10(-9) and in combined samples (rs2523722 p combined = 2.88 × 10(-16)) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study. CONCLUSIONS: This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci.

Original publication

DOI

10.1016/j.biopsych.2012.05.035

Type

Journal article

Journal

Biol Psychiatry

Publication Date

15/10/2012

Volume

72

Pages

620 - 628

Keywords

Adult, Aged, Aged, 80 and over, Calcium Channels, T-Type, Databases, Genetic, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, HLA-C Antigens, Humans, Ireland, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Schizophrenia, Young Adult