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.
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.
Authors: Leigh A Needleman; Xiao-Bo Liu; Faten El-Sabeawy; Edward G Jones; A Kimberley McAllister Journal: Proc Natl Acad Sci U S A Date: 2010-09-13 Impact factor: 11.205
Authors: Jian Yang; Michael N Weedon; Shaun Purcell; Guillaume Lettre; Karol Estrada; Cristen J Willer; Albert V Smith; Erik Ingelsson; Jeffrey R O'Connell; Massimo Mangino; Reedik Mägi; Pamela A Madden; Andrew C Heath; Dale R Nyholt; Nicholas G Martin; Grant W Montgomery; Timothy M Frayling; Joel N Hirschhorn; Mark I McCarthy; Michael E Goddard; Peter M Visscher Journal: Eur J Hum Genet Date: 2011-03-16 Impact factor: 4.246
Authors: Gonçalo R Abecasis; David Altshuler; Adam Auton; Lisa D Brooks; Richard M Durbin; Richard A Gibbs; Matt E Hurles; Gil A McVean Journal: Nature Date: 2010-10-28 Impact factor: 49.962
Authors: Céline Bellenguez; Amy Strange; Colin Freeman; Peter Donnelly; Chris C A Spencer Journal: Bioinformatics Date: 2011-11-03 Impact factor: 6.937
Authors: A K Merikangas; R Segurado; E Kelleher; D Hogan; C Delaney; M Gill; L Gallagher; A P Corvin; E A Heron Journal: Mol Psychiatry Date: 2015-08-25 Impact factor: 15.992
Authors: Alexis C Edwards; Tim B Bigdeli; Anna R Docherty; Silviu Bacanu; Donghyung Lee; Teresa R de Candia; Arden Moscati; Dawn L Thiselton; Brion S Maher; Brandon K Wormley; Dermot Walsh; Francis A O'Neill; Kenneth S Kendler; Brien P Riley; Ayman H Fanous Journal: Schizophr Bull Date: 2015-08-27 Impact factor: 9.306
Authors: E M Kenny; P Cormican; S Furlong; E Heron; G Kenny; C Fahey; E Kelleher; S Ennis; D Tropea; R Anney; A P Corvin; G Donohoe; L Gallagher; M Gill; D W Morris Journal: Mol Psychiatry Date: 2013-10-15 Impact factor: 15.992
Authors: Elizabeth A Heron; Paul Cormican; Gary Donohoe; Francis A O'Neill; Kenneth S Kendler; Brien P Riley; Michael Gill; Aiden P Corvin; Derek W Morris Journal: Schizophr Res Date: 2014-02-20 Impact factor: 4.939
Authors: Francesca Canellas; Ling Lin; Maria Rosa Julià; Antonio Clemente; Cristofol Vives-Bauza; Hanna M Ollila; Seung Chul Hong; Susana M Arboleya; Mali A Einen; Juliette Faraco; Marcelo Fernandez-Vina; Emmanuel Mignot Journal: J Clin Sleep Med Date: 2014-09-15 Impact factor: 4.062
Authors: A Hargreaves; R Anney; C O'Dushlaine; K K Nicodemus; M Gill; A Corvin; D Morris; Gary Donohoe Journal: Psychol Med Date: 2013-11-28 Impact factor: 7.723
Authors: Angela Heck; Matthias Fastenrath; Sandra Ackermann; Bianca Auschra; Horst Bickel; David Coynel; Leo Gschwind; Frank Jessen; Hanna Kaduszkiewicz; Wolfgang Maier; Annette Milnik; Michael Pentzek; Steffi G Riedel-Heller; Stephan Ripke; Klara Spalek; Patrick Sullivan; Christian Vogler; Michael Wagner; Siegfried Weyerer; Steffen Wolfsgruber; Dominique J-F de Quervain; Andreas Papassotiropoulos Journal: Neuron Date: 2014-02-13 Impact factor: 17.173
Authors: Z Hawi; T D R Cummins; J Tong; M Arcos-Burgos; Q Zhao; N Matthews; D P Newman; B Johnson; A Vance; H S Heussler; F Levy; S Easteal; N R Wray; E Kenny; D Morris; L Kent; M Gill; M A Bellgrove Journal: Mol Psychiatry Date: 2016-07-26 Impact factor: 15.992