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

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 χ 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 ( χ 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