PMID- 22883433 OWN - NLM STAT- MEDLINE DCOM- 20130227 LR - 20231104 IS - 1873-2402 (Electronic) IS - 0006-3223 (Print) IS - 0006-3223 (Linking) VI - 72 IP - 8 DP - 2012 Oct 15 TI - Genome-wide association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia. PG - 620-8 LID - S0006-3223(12)00554-9 [pii] LID - 10.1016/j.biopsych.2012.05.035 [doi] AB - 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 x 10(-9) and in combined samples (rs2523722 p combined = 2.88 x 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. CI - Copyright (c) 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. CN - Irish Schizophrenia Genomics Consortium and the Wellcome Trust Case Control Consortium 2 LA - eng GR - 068545/Z/02/WT_/Wellcome Trust/United Kingdom GR - MH083094/MH/NIMH NIH HHS/United States GR - 085475/B/08/Z/WT_/Wellcome Trust/United Kingdom GR - 075491/Z/04/B/HHMI/Howard Hughes Medical Institute/United States GR - MH 41953/MH/NIMH NIH HHS/United States GR - 090532/WT_/Wellcome Trust/United Kingdom GR - 085475/Z/08/Z/WT_/Wellcome Trust/United Kingdom GR - 072894/Z/03/Z/HHMI/Howard Hughes Medical Institute/United States GR - R01 MH041953/MH/NIMH NIH HHS/United States GR - G0000934/MRC_/Medical Research Council/United Kingdom GR - 090532/Z/09/Z/WT_/Wellcome Trust/United Kingdom GR - R01 MH083094/MH/NIMH NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120809 PL - United States TA - Biol Psychiatry JT - Biological psychiatry JID - 0213264 RN - 0 (CACNA1I protein, human) RN - 0 (Calcium Channels, T-Type) RN - 0 (HLA-C Antigens) RN - 0 (HLA-C*01:02 antigen) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Calcium Channels, T-Type MH - Databases, Genetic/statistics & numerical data MH - Female MH - *Genetic Predisposition to Disease MH - Genome-Wide Association Study MH - Genotype MH - HLA-C Antigens/*genetics MH - Humans MH - Ireland MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Risk Factors MH - Schizophrenia/*genetics MH - Young Adult PMC - PMC3529467 MID - NIHMS428997 COIS- The authors report no biomedical financial interests or potential conflicts of interest. FIR - Donnelly, Peter IR - Donnelly P FIR - Barroso, Ines IR - Barroso I FIR - Blackwell, Jenefer M IR - Blackwell JM FIR - Bramon, Elvira IR - Bramon E FIR - Brown, Matthew A IR - Brown MA FIR - Casas, Juan P IR - Casas JP FIR - Corvin, Aiden IR - Corvin A FIR - Deloukas, Panos IR - Deloukas P FIR - Duncanson, Audrey IR - Duncanson A FIR - Jankowski, Janusz IR - Jankowski J FIR - Markus, Hugh S IR - Markus HS FIR - Mathew, Christopher G IR - Mathew CG FIR - Palmer, Colin N A IR - Palmer CN FIR - Plomin, Robert IR - Plomin R FIR - Rautanen, Anna IR - Rautanen A FIR - Sawcer, Stephen J IR - Sawcer SJ FIR - Trembath, Richard C IR - Trembath RC FIR - Viswanathan, Ananth C IR - Viswanathan AC FIR - Wood, Nicholas W IR - Wood NW FIR - Spencer, Chris C A IR - Spencer CC FIR - Band, Gavin IR - Band G FIR - Bellenguez, Celine IR - Bellenguez C FIR - Dilthey, Alexander IR - Dilthey A FIR - Freeman, Colin IR - Freeman C FIR - Hellenthal, Garrett IR - Hellenthal G FIR - Giannoulatou, Eleni IR - Giannoulatou E FIR - McVean, Gil IR - McVean G FIR - Moutsianas, Loukas IR - Moutsianas L FIR - Pirinen, Matti IR - Pirinen M FIR - Pearson, Richard IR - Pearson R FIR - Strange, Amy IR - Strange A FIR - Su, Zhan IR - Su Z FIR - Tashakkori-Ghanbaria, Avazeh IR - Tashakkori-Ghanbaria A FIR - Vukcevic, Damjan IR - Vukcevic D FIR - Donnelly, Peter IR - Donnelly P FIR - Langford, Cordelia IR - Langford C FIR - Hunt, Sarah E IR - Hunt SE FIR - Edkins, Sarah IR - Edkins S FIR - Gwilliam, Rhian IR - Gwilliam R FIR - Blackburn, Hannah IR - Blackburn H FIR - Bumpstead, Suzannah J IR - Bumpstead SJ FIR - Dronov, Serge IR - Dronov S FIR - Gillman, Matthew IR - Gillman M FIR - Gray, Emma IR - Gray E FIR - Hammond, Naomi IR - Hammond N FIR - Jayakumar, Alagurevathi IR - Jayakumar A FIR - McCann, Owen T IR - McCann OT FIR - Liddle, Jennifer IR - Liddle J FIR - Potter, Simon C IR - Potter SC FIR - Ravindrarajah, Radhi IR - Ravindrarajah R FIR - Ricketts, Michelle IR - Ricketts M FIR - Waller, Matthew IR - Waller M FIR - Weston, Paul IR - Weston P FIR - Widaa, Sara IR - Widaa S FIR - Whittaker, Pamela IR - Whittaker P FIR - Barroso, Ines IR - Barroso I FIR - Deloukas, Panos IR - Deloukas P FIR - Riley, Brien P IR - Riley BP FIR - Morris, Derek W IR - Morris DW FIR - O'Dushlaine, T IR - O'Dushlaine T FIR - Maher, Brion S IR - Maher BS FIR - Cormican, Paul IR - Cormican P FIR - Kenny, Elaine M IR - Kenny EM FIR - Wormley, Brandon IR - Wormley B FIR - Donohoe, Gary IR - Donohoe G FIR - Quinn, Emma IR - Quinn E FIR - Judge, Roisin IR - Judge R FIR - Coleman, Kim IR - Coleman K FIR - Tropea, Daniela IR - Tropea D FIR - Roche, Siobhan IR - Roche S FIR - Cummings, Liz IR - Cummings L FIR - Kelleher, Eric IR - Kelleher E FIR - McKeon, Patrick IR - McKeon P FIR - Dinan, Ted IR - Dinan T FIR - McDonald, Colm IR - McDonald C FIR - Murphy, Kieran C IR - Murphy KC FIR - O'Callaghan, Eadbhard IR - O'Callaghan E FIR - O'Neill, Francis A IR - O'Neill FA FIR - Waddington, John L IR - Waddington JL FIR - Walsh, Dermot IR - Walsh D FIR - Stone, Jennifer IR - Stone J FIR - Scolnick, Ed IR - Scolnick E FIR - Purcell, Shaun IR - Purcell S FIR - Sklar, Pamela IR - Sklar P FIR - Ripke, Stephan IR - Ripke S FIR - Walters, James IR - Walters J FIR - Owen, Michael J IR - Owen MJ FIR - O'Donovan, Michael C IR - O'Donovan MC FIR - Kendler, Ken S IR - Kendler KS FIR - Corvin, Aiden IR - Corvin A FIR - Gill, Michael IR - Gill M EDAT- 2012/08/14 06:00 MHDA- 2013/02/28 06:00 PMCR- 2012/12/24 CRDT- 2012/08/14 06:00 PHST- 2012/01/12 00:00 [received] PHST- 2012/05/01 00:00 [revised] PHST- 2012/05/01 00:00 [accepted] PHST- 2012/08/14 06:00 [entrez] PHST- 2012/08/14 06:00 [pubmed] PHST- 2013/02/28 06:00 [medline] PHST- 2012/12/24 00:00 [pmc-release] AID - S0006-3223(12)00554-9 [pii] AID - 10.1016/j.biopsych.2012.05.035 [doi] PST - ppublish SO - Biol Psychiatry. 2012 Oct 15;72(8):620-8. doi: 10.1016/j.biopsych.2012.05.035. Epub 2012 Aug 9.