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Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia

Molecular Psychiatry volume 11, pages 384–394 (2006)Cite this article

Abstract

The orphan G protein-coupled receptor 78 (GPR78) gene lies within a region of chromosome 4p where we have previously shown linkage to bipolar affective disorder (BPAD) in a large Scottish family. GPR78 was screened for single-nucleotide polymorphisms (SNPs) and a linkage disequilibrium map was constructed. Six tagging SNPs were selected and tested for association on a sample of 377 BPAD, 392 schizophrenia (SCZ) and 470 control individuals. Using standard χ2 statistics and a backwards logistic regression approach to adjust for the effect of sex, SNP rs1282, located approximately 3 kb upstream of the coding region, was identified as a potentially important variant in SCZ (χ2 P=0.044; LRT P=0.065). When the analysis was restricted to females, the strength of association increased to an uncorrected allele P-value of 0.015 (odds ratios (OR)=1.688, 95% confidence intervals (CI): 1.104–2.581) and uncorrected genotype P-value of 0.015 (OR=5.991, 95% CI: 1.545–23.232). Under the recessive model, the genotype P-value improved further to 0.005 (OR=5.618, 95% CI: 1.460–21.617) and remained significant after correcting for multiple testing (P=0.017). No single-marker association was detected in the SCZ males, in the BPAD individuals or with any other SNP. Haplotype analysis of the case–control samples revealed several global and individual haplotypes, with P-values <0.05, all but one of which contained SNP rs1282. After correcting for multiple testing, two haplotypes remained significant in both the female BPAD individuals (P=0.038 and 0.032) and in the full sample of affected female individuals (P=0.044 and 0.033). Our results provide preliminary evidence for the involvement of GPR78 in susceptibility to BPAD and SCZ in the Scottish population.

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Acknowledgements

We would like to thank the Sanger Institute and the Genetics Core of the Wellcome Trust Clinical Research Facility at the Western General Hospital for carrying out the SNP genotyping; M Walker and M van Beck for assistance with clinical aspects of the study and ST Cooper for assistance in the preparation of the manuscript. A Tenesa acknowledges funding from Cancer Research UK. This work was supported by grants from the Medical Research Council. This work was supported by the UK Medical Research Council.

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  1. S L Underwood and A Christoforou: These authors contributed equally to this work.

Authors and Affiliations

  1. Medical Genetics Section, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Edinburgh, UK

    S L Underwood, A Christoforou, P A Thomson, N R Wray, R A Adams, S Le Hellard, S W Morris, D J Porteous & K L Evans

  2. MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK

    A Tenesa

  3. Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK

    J Whittaker

  4. Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK

    D H R Blackwood & W J Muir

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Correspondence to A Christoforou.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Underwood, S., Christoforou, A., Thomson, P. et al. Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia. Mol Psychiatry 11, 384–394 (2006). https://doi.org/10.1038/sj.mp.4001786

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