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

S L Underwood, A Christoforou, P A Thomson, N R Wray, A Tenesa, J Whittaker, R A Adams, S Le Hellard, S W Morris, D H R Blackwood, W J Muir, D J Porteous, K L Evans

Research output: Contribution to journalArticlepeer-review

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 chi(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
Original languageEnglish
Pages (from-to)384-94
Number of pages11
JournalMolecular Psychiatry
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 2006

Keywords

  • Bipolar Disorder
  • Case-Control Studies
  • Chi-Square Distribution
  • Chromosome Mapping
  • Chromosomes, Human, Pair 4
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Lod Score
  • Logistic Models
  • Male
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Schizophrenia
  • Sex Factors

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