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<sup>2</sup> = 89.2%] and rs1426217 [OR = 1.13 (95% CI) = 0.64-2.0, I<sup>2</sup> = 83%].
One 15q11-q13 locus encodes the GABA(A) receptor β3 subunit gene (GABRB3), which has been implicated by several studies in both autism and absence epilepsy, and the co-morbidity of epilepsy in autism is well established.
The association and linkage study for the gamma-aminobutyric acid type A receptor beta3 subunit gene (GABRB3), located within the chromosome 15q11-q13 autism candidate region, and ASD have been evaluated.
Examining paternal transmissions only, we found marginal evidence for LD with a protective allele at marker D15S11 in the ASD families (Chi-sq 7 df, P = 0.05) and marginal evidence for risk alleles at markers D15S1506 (Chi-sq 13.7, 6 df, P = 0.06), GABRB3 (Chi-sq 15.9, 8 df, P = 0.11) and D15S1002 (Chi-sq 17.7, 9 df, P = 0.08) in the autism only families.
These results suggest an overlapping pathway of gene dysregulation within 15q11-q13 in Rett, Angelman and autism and implicate MeCP2 in the regulation of UBE3A and GABRB3 expressions in the postnatal mammalian brain.
We have screened the families of the Collaborative Linkage Study of Autism for several markers spanning a candidate region covering approximately 2 Mb and including the Angelman syndrome gene (UBE3A) and a cluster of gamma-aminobutyric acid (GABA(A)) receptor subunit genes (GABRB3, GABRA5, and GABRG3).
Three of the GABAA receptor subunit genes (GABRB3, GABRA5 and GABRG3) form a cluster on chromosome 15q11-q13, in a region that has been genetically associated with autistic disorder (AutD).
No significant evidence of association or linkage was found at any of the markers tested, indicating that the 5-HTT and the GABRB3 genes are unlikely to play a major role in the aetiology of autism in our family data set.
Chromosome 15q11-q13 has been implicated in the genetic etiology of AD based on (1) cytogenetic abnormalities; (2) increased recombination frequency in this region in AD versus non-AD families; (3) suggested linkage with markers D15S156, D15S219, and D15S217; and (4) evidence for significant association with polymorphisms in the gamma-aminobutyric acid receptor subunit B3 gene (GABRB3).
The convergence of GABRB3 as a positional and functional candidate along with the linkage-disequilibrium data suggests the need for further investigation of the role of GABRB3 or adjacent genes in autistic disorder.
The convergence of GABRB3 as a positional and functional candidate along with the linkage-disequilibrium data suggests the need for further investigation of the role of GABRB3 or adjacent genes in autistic disorder.