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No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF)

Molecular Psychiatry volume 9, pages 777–783 (2004)Cite this article

Abstract

The neuregulin-1 gene (NRG1) at chromosome 8p21–22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.

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Acknowledgements

We acknowledge all families participating in this study. We also thank Michael Gill and coworkers for access to their NRG1 association data prior to publication.14 This work was supported by NIH Grants No. MH-41953 and MH-45390.

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Authors and Affiliations

  1. Department of Psychiatry, Virginia Institute of Psychiatric and Behavioural Genetics, Virginia Commonwealth University, Richmond, VA, USA

    D L Thiselton, B T Webb, B M Neale, R C Ribble, B P Riley & K S Kendler

  2. Department of Psychiatry, The Queens University, Belfast, Northern Ireland

    F A O'Neill

  3. The Health Research Board, Dublin, Ireland

    D Walsh

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  1. D L Thiselton
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  2. B T Webb
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  7. B P Riley
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  8. K S Kendler
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Correspondence to D L Thiselton.

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Thiselton, D., Webb, B., Neale, B. et al. No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF). Mol Psychiatry 9, 777–783 (2004). https://doi.org/10.1038/sj.mp.4001530

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