Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia
In: Molecular psychiatry, Jg. 11 (2006), Heft 4, S. 386-394
Online
academicJournal
- print; 9; 55 ref
Zugriff:
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 Χ2statistics and a backwards logistic regression approach to adjust for the effect of sex, SNP rs1282, located approximately 3kb upstream of the coding region, was identified as a potentially important variant in SCZ (x2 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 (Cl): 1.104-2.581) and uncorrected genotype P-value of 0.015 (OR=5.991, 95% Cl: 1.545-23.232). Under the recessive model, the genotype P-value improved further to 0.005 (OR=5.618, 95% Cl: 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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Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia
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Autor/in / Beteiligte Person: | UNDERWOOD, S. L ; CHRISTOFOROU, A ; MUIR, W. J ; PORTEOUS, D. J ; EVANS, K. L ; THOMSON, P. A ; WRAY, N. R ; TENESA, A ; WHITTAKER, J ; ADAMS, R. A ; LE HELLARD, S ; MORRIS, S. W ; BLACKWOOD, D. H. R |
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Zeitschrift: | Molecular psychiatry, Jg. 11 (2006), Heft 4, S. 386-394 |
Veröffentlichung: | Basingstoke: Nature Publishing Group, 2006 |
Medientyp: | academicJournal |
Umfang: | print; 9; 55 ref |
ISSN: | 1359-4184 (print) |
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