TY - JOUR
T1 - Genome-wide association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia
AU - Wellcome Trust Case Control Consortium 2
AU - Donnelly, Peter
AU - Barroso, Ines
AU - Blackwell, Jenefer M.
AU - Bramon, Elvira
AU - Brown, Matthew A.
AU - Casas, Juan P.
AU - Corvin, Aiden
AU - Deloukas, Panos
AU - Duncanson, Audrey
AU - Jankowski, Janusz
AU - Markus, Hugh S.
AU - Mathew, Christopher G.
AU - Palmer, Colin N.A.
AU - Plomin, Robert
AU - Rautanen, Anna
AU - Sawcer, Stephen J.
AU - Trembath, Richard C.
AU - Viswanathan, Ananth C.
AU - Wood, Nicholas W.
AU - Spencer, Chris C.A.
AU - Band, Gavin
AU - Bellenguez, Céline
AU - Dilthey, Alexander
AU - Freeman, Colin
AU - Hellenthal, Garrett
AU - Giannoulatou, Eleni
AU - McVean, Gil
AU - Moutsianas, Loukas
AU - Pirinen, Matti
AU - Pearson, Richard
AU - Strange, Amy
AU - Su, Zhan
AU - Tashakkori-Ghanbaria, Avazeh
AU - Vukcevic, Damjan
AU - Langford, Cordelia
AU - Hunt, Sarah E.
AU - Edkins, Sarah
AU - Gwilliam, Rhian
AU - Blackburn, Hannah
AU - Bumpstead, Suzannah J.
AU - Dronov, Serge
AU - Gillman, Matthew
AU - Gray, Emma
AU - Hammond, Naomi
AU - Jayakumar, Alagurevathi
AU - McCann, Owen T.
AU - Liddle, Jennifer
AU - Potter, Simon C.
AU - Ravindrarajah, Radhi
AU - Ricketts, Michelle
PY - 2012/10/15
Y1 - 2012/10/15
N2 - 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.
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 × 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.
KW - CACNA1I
KW - genetics
KW - genome-wide association study
KW - HLAC
KW - major histocompatibility complex
KW - polygene score
KW - schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84866616686&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2012.05.035
DO - 10.1016/j.biopsych.2012.05.035
M3 - Article
C2 - 22883433
AN - SCOPUS:84866616686
SN - 0006-3223
VL - 72
SP - 620
EP - 628
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 8
ER -