Study Report

Reference	Underwood, S. L., 2006 PMID: 16389273
Citation	Underwood, S. L., A. Christoforou, et al. (2006). "Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia." Mol Psychiatry 11(4): 384-394.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	377 BPAD, 392 schizophrenia (SCZ) and 470 control individuals
SNP/Region/Marker Size	6 SNPs
Predominant Ethnicity	Caucasian
Population	Scottish
Gender	163 males, 214 females wih BD, 280 males, 112 females with SZ, 244 males, 223 females, three unknowns of controls

Sample Diagnosis	DSM-IV and ICD-10
Sample Status	Individuals suffering from BPAD or SCZ were recruited from in-patient and outpatient services at the Royal Edinburgh and other Scottish psychiatric hospitals. All were screened using the semistructured Schedule for Affective Disorder and Schizophrenia- Lifetime version (SADS-L)24 interview schedule by psychiatrists experienced in its use.
Technique	genotyped at the Sanger Institute by the MASSARRAYt primer extension method
Statistical Method	Differences in allele and genotype frequencies between cases and controls were evaluated with the chi square-test of independence (with 1 and 2 degrees of freedom, respectively). Fisher's exact test, as implemented in SISA, was used when appropriate, for sparse contingency tables. Significance was initially declared at a nominal P value of 0.05. The significance of the odds ratios (ORs) was determined using a z-statistic. Haplotype frequency estimation and comparison was carried out using the statistical analysis program COCAPHASE 2.4339.
Result Summary	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 <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.