Genome-Wide Association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia

Strange, Amy, Riley, Brien P., Spencer, Chris C. A., Morris, Derek W., Pirinen, Matti, O'Dushlaine, Colm T., Su, Zhan, Maher, Brion S., Freeman, Colin, Cormican, Paul, Bellenguez, Celine, Kenny, Elaine M., Band, Gavin, Wormley, Brandon, Donohoe, Gary, Dilthey, Alexander, Moutsianas, Loukas, Quinn, Emma, Edkins, Sarah, Judge, Roisin, Coleman, Kim, Hunt, Sarah, Tropea, Daniela, Roche, Siobhan, Cummings, Liz, Kelleher, Eric, McKeon, Patrick, Dinan, Ted, McDonald, Colm, Murphy, Kieran C., O'Callaghan, Eadbhard, O'Neill, Francis A., Waddington, John L., Walsh, Dermot, Giannoulatou, Eleni, Langford, Cordelia, Deloukas, Panos, Gray, Emma, Dronov, Serge, Potter, Simon, Pearson, Richard, Vukcevic, Damjan, Tashakkori-Ghanbaria, Avazeh, Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S., Mathew, Christopher G., Palmer, Colin N. A., Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J., Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas W., Stone, Jennifer, Scolnick, Ed, Purcell, Shaun, Sklar, Pamela, Ripke, Stephan, Walters, James, Owen, Michael J., O'Donovan, Michael C., Peltonen, Leena, McVean, Gil, Kendler, Ken S., Gill, Michael, Donnelly, Peter and Corvin, Aiden (2012) 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: 620-628. doi:10.1016/j.biopsych.2012.05.035

Author Strange, Amy
Riley, Brien P.
Spencer, Chris C. A.
Morris, Derek W.
Pirinen, Matti
O'Dushlaine, Colm T.
Su, Zhan
Maher, Brion S.
Freeman, Colin
Cormican, Paul
Bellenguez, Celine
Kenny, Elaine M.
Band, Gavin
Wormley, Brandon
Donohoe, Gary
Dilthey, Alexander
Moutsianas, Loukas
Quinn, Emma
Edkins, Sarah
Judge, Roisin
Coleman, Kim
Hunt, Sarah
Tropea, Daniela
Roche, Siobhan
Cummings, Liz
Kelleher, Eric
McKeon, Patrick
Dinan, Ted
McDonald, Colm
Murphy, Kieran C.
O'Callaghan, Eadbhard
O'Neill, Francis A.
Waddington, John L.
Walsh, Dermot
Giannoulatou, Eleni
Langford, Cordelia
Deloukas, Panos
Gray, Emma
Dronov, Serge
Potter, Simon
Pearson, Richard
Vukcevic, Damjan
Tashakkori-Ghanbaria, Avazeh
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Duncanson, Audrey
Jankowski, Janusz
Markus, Hugh S.
Mathew, Christopher G.
Palmer, Colin N. A.
Plomin, Robert
Rautanen, Anna
Sawcer, Stephen J.
Trembath, Richard C.
Viswanathan, Ananth C.
Wood, Nicholas W.
Stone, Jennifer
Scolnick, Ed
Purcell, Shaun
Sklar, Pamela
Ripke, Stephan
Walters, James
Owen, Michael J.
O'Donovan, Michael C.
Peltonen, Leena
McVean, Gil
Kendler, Ken S.
Gill, Michael
Donnelly, Peter
Corvin, Aiden
Total Author Count Override 209
Title Genome-Wide Association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
Publication date 2012-10
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2012.05.035
Volume 72
Issue 8
Start page 620
End page 628
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2013
Language eng
Formatted abstract
We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia.


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.


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.


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.
Keyword Cacna1I
Genome-wide association study
Major histocompatibility complex
Polygene score
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
UQ Diamantina Institute Publications
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