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Annotation

[No authors listed]. Genome-wide association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia. Biol Psychiatry . 2012 Oct 15 ; 72(8):620-8. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Patrick Sullivan, SRF Advisor
Submitted 30 August 2012 Posted 30 August 2012

This is an important new study from the Irish Schizophrenia Genomics Consortium and the second wave of the Wellcome Trust Case-Control Consortium (WTCCC).

The study is notable, as it found genomewide significance for an association of schizophrenia with genetic variation in the major histocompatibility locus (MHC). Given concerns about stratification effects at this locus, it is notable that this association was significant in a sample from a single country with relatively homogeneous ancestry. Prior studies had combined data from multiple different countries, and these results provide an important consistency check.

In addition, the authors provide important suggestive evidence for a specific variant in a class 1 MHC locus (HLA-C gene, the "01:02" variant, p = 3e-4).

The use of 1000 Genomes Project data for imputation is notable for the improved signal pattern it appeared to afford.

View all comments by Patrick Sullivan


Comment by:  Monojit Debnath
Submitted 29 August 2012 Posted 31 August 2012
  I recommend this paper

The newly reported HLA-C*01:02 as a risk factor of schizophrenia by Strange et al., 2012, in this GWAS (Irish Schizophrenia Genomics Consortium & the Wellcome Trust Case Control Consortium) is a significant contribution and has further strengthened MHC’s role in schizophrenia. Although multiple GWAS in various populations have implicated MHC as a major and best replicated risk loci of schizophrenia (as reviewed in Debnath et al., 2012), the findings remained inconclusive.

Strange et al. (2012), in this GWAS on 1,606 schizophrenia patients and 1,794 controls, found association of three SNPs (rs204999, rs2523722, and rs7746922) within the MHC region with schizophrenia, of which the most significant association was with rs204999. They also replicated this study by considering some selected SNPs in a large, independent set of 13,195 schizophrenia patients and 31,021 controls. In the combined samples (this GWAS and replication data), rs2523722 appeared as the most significantly associated MHC variant. Intriguingly, these findings...  Read more


View all comments by Monojit Debnath
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