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


Underwood, SL; Christoforou, A; Thomson, PA; Wray, NR; Tenesa, A; Whittaker, J; Adams, RA; le Hellard, S; Morris, SW; Blackwood, DHR; Muir, WJ; Porteous, DJ; Evans, KL; (2006) Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia. Molecular psychiatry, 11 (4). pp. 384-394. ISSN 1359-4184 DOI: https://doi.org/10.1038/sj.mp.4001786

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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 v 2 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 (chi(2) 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.

Item Type: Article
Keywords: bipolar disorder, schizophrenia, G protein-coupled receptors, association study, linkage disequilibrium, Protein-coupled receptor, linkage disequilibrium, mood disorders, genome scan, locus, susceptibility, sequence, axis, tool, pathophysiology
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 16389273
Web of Science ID: 236339700008
URI: http://researchonline.lshtm.ac.uk/id/eprint/11998

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