Association of SNPs and haplotypes in GABRB2 with schizophrenia in Japanese and German‐Caucasians

Abstract

SNPs and haplotypes in Intron 7 of GABAA receptor β2 gene (GABRB2) were previously found to be associated with schizophrenia in Han Chinese. In the present study, cross-validation of this finding was performed with two ethnically-divergent groups: Japanese (JP) and German Caucasian (GE). SNP genotyping was achieved through resequencing of 1,839-bp, harboring the positively-associated SNPs. For disease association, all possible combinations of selected tagging-SNPs were analyzed with Bonferroni-correction and permutation. Random re-sampling was applied to generate size- and gender-balanced samples. Seventeen SNPs, including six newly-discovered, were revealed (0.93% density). Linkage disequilibrium (LD) maps illustrated at least two low LD points, common to the two populations. Strong disease associations of SNP combinations were demonstrated in JP (P = 0.0002 – 0.0191) and GE (P = 0.0033 – 0.0410). They were found largely convergent to SNP combinations with rs1816072 and rs1816071 in both populations. Among the clinical subtypes, the more significant association was observed with systematic schizophrenia. The present study thus provides a multi-population validation of disease association with GABRB2 and places emphasis on the potential role of this gene in schizophrenia etiology. This study was supported by the University Grants Council and the Innovations and Technology Fund of Hong Kong.