Meta-Analysis of the Association between GABA Receptor Polymorphisms and Autism Spectrum Disorder (ASD)

Abstract

Previous studies have reported the association of GABA receptor subunits B3, A5, and G3 single-nucleotide polymorphisms (SNPs) in chromosome 15q11-q13 with autism spectrum disorders (ASDs). However, the currently available results are inconsistent. This study aimed to investigate the association between ASD and the GABA receptor SNPs in chromosomal region 15q11-q13. The association was calculated by the overall odds ratio (OR) with a 95 confidence interval (CI). We used sensitivity analyses and the assessment of publication bias in our meta-analysis. Eight independent case-control studies involving 1408 cases and 2846 healthy controls were analyzed, namely, 8 studies for GABRB3 SNPs as well as 4 studies for GABRA5 and GABRG3 polymorphisms. The meta-analysis showed that GABRB3 polymorphisms in general are not significantly associated with autism OR = 0.846 (95% CI): 0.595-1.201, I-2 = 79.1%. Further analysis indicated that no associations were found between GABRB3 SNPs and autism on rs2081648 OR = 0.84 (95% CI) = 0.41-1.72, I-2 = 89.2% and rs1426217 OR = 1.13 (95% CI) = 0.64-2.0, I-2 = 83%. An OR of 0.95 (95% CI) = 0.77-1.17 was reported (I-2 = 0.0%) for GABRA5 SNPs and an OR of 0.96 (95% CI) = 0.24-3.81 was obtained from GABRG3 SNPs (I-2 = 97.8%). This meta-analysis provides strong evidence that different SNPs of GABA receptor B3, A5, and G3 subunit genes located on chromosome 15q11-q13 are not associated with the development of autism spectrum diseases in different ethnic populations. However, in future research, large-scale and high-quality studies are necessary to confirm the results.