No evidence for significant association between GABA receptor genes in chromosome 15q11-q13 and autism in a Japanese population.

The gamma-aminobutyric acid (GABA) receptor genes GABRB3, GABRA5, and GABRG3 located on chromosome 15q11-q13 have been major candidates for susceptibility genes for autism, a neurodevelopmental disorder with a complex genetic etiology. In this study, we first investigated the association between the GABA receptor genes and autism in a Japanese population by analyzing 11 single nucleotide polymorphisms (SNPs). Intron 3 of GABRB3 was densely mapped because the previous studies observed the association of the microsatellite 155CA-2 located in the region. We observed no significant difference in allelic frequencies or genotypic distributions of the 11 SNPs between patients and controls. A permutation test showed no significant global differences in estimated haplotype frequencies between patients and controls. Analysis after confining the subjects to males showed similar results. Thus, this study provides no positive evidence of an association between the GABA receptor genes and autism in a Japanese population. However, in a SNP (rs3212337) located near the microsatellite 155CA-2, a significant deviation from the Hardy-Weinberg equilibrium was observed in patients (p = 0.029, corrected for multiple testing). This finding may suggest further studies around the markers for more definitive conclusions.