Abstract
Two recent association studies have implicated the neuregulin-1 gene (NRG1) at chromosome 8p21–22 as a susceptibility gene for schizophrenia. Stefansson et al identified three ‘at-risk’ haplotypes (HapA, B and C) which spanned the NRG1 locus and shared a common core haplotype. Subsequently, they demonstrated evidence that the core haplotype was associated with schizophrenia in an independent Scottish sample. To confirm and refine this haplotype we investigated the NRG1 locus in an independent Irish case–control sample. We did not find the core haplotype to be associated in our sample. However, we identified a refined 2-marker haplotype (HapBIRE) that shared common alleles with one of the Icelandic ‘at-risk’ haplotypes and is in significant excess in the Irish cases (19.4%) vs controls (12.3%) (P=0.013). This refined ‘at-risk’ haplotype is also in significant excess in the Scottish case sample (17.0% vs 13.5%; P=0.036). Interestingly, this refined ‘at-risk’ haplotype is positioned close to an EST cluster of unknown function (Hs.97362) within intron 1 of NRG1.
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Acknowledgements
The authors gratefully acknowledge the contribution of all participating individuals and institutions in this study. Dr Corvin is a Wellcome Trust Research Fellow in Mental Health. The authors would like to thank the Health Research Board (Ireland), Science Foundation Ireland, Health Education Authority (Ireland) and the Stanley Medical Research Institute (USA) for their support of this research. The authors also gratefully acknowledge deCODE Genetics for their technical assistance.
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Corvin, A., Morris, D., McGhee, K. et al. Confirmation and refinement of an ‘at-risk’ haplotype for schizophrenia suggests the EST cluster, Hs.97362, as a potential susceptibility gene at the Neuregulin-1 locus. Mol Psychiatry 9, 208–212 (2004). https://doi.org/10.1038/sj.mp.4001412
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DOI: https://doi.org/10.1038/sj.mp.4001412
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