Genome-wide association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia.
Item Type:Journal Article
Citation:Strange A, Riley BP, Spencer CA, Morris DW, Pirinen M, O'Dushlaine CT, Su Z, Maher BS, Freeman C, Cormican P, Bellenguez C, Kenny EM, Band G, Wormley B, Donohoe G, Dilthey A, Moutsianas L,Quinn E, Edkins S, Judge R, Coleman K, Hunt S, Tropea D, Roche S, Cummings L, Kelleher E, McKeon P, Dinan T, McDonald C, Murphy KC, O'Callaghan E, O'Neill FA, Waddington JL, Walsh D, Giannoulatou E, Langford C, Deloukas P, Gray E, Dronov S, Potter S, Pearson R, Vukcevic D, Tashakkori-Ghanbaria A, Blackwell JM,15, Bramon E, Brown MA, Casas JP, Duncanson A, Jankowski J, Markus HS, Mathew CG, Palmer CNA, Plomin RP, Rautanen A, Sawcer SJ, Trembath RC, Viswanathan AC, Wood NW, Stone J, Scolnick E, Purcell S, Sklar P, SGENE+ Consortium, Ripke S, Walters J, Owen MJ, O'Donovan MC, Schizophrenia Working Group of the Psychiatric GWAS Consortium, Peltonen L, McVean G, Kendler KS, Gill M, Donnelly P, Corvin A for Irish Schizophrenia Genomics Consortium and the Wellcome Trust Case Control Consortium 2, Genome-wide association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia., Biological Psychiatry, 72, 8, 2012, 620-628
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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
Type of material:Journal Article
Series/Report no:Biological Psychiatry;
Availability:Full text available