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Evidence for Interaction Between Markers in GABA ( A ) Receptor Subunit Genes in an A rgentinean Autism Spectrum Disorder Population
Author(s) -
Sesarini Carla V.,
Costa Lucas,
Naymark Muriel,
Grañaora,
Cajal Andrea R.,
García Coto Miguel,
Pallia Roberto C.,
Argibay Pablo F.
Publication year - 2014
Publication title -
autism research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.656
H-Index - 66
eISSN - 1939-3806
pISSN - 1939-3792
DOI - 10.1002/aur.1353
Subject(s) - autism , single nucleotide polymorphism , multifactor dimensionality reduction , genetics , autism spectrum disorder , heritability of autism , population , snp , allele frequency , allele , haplotype , genetic association , zolpidem , biology , minor allele frequency , genotype , gene , psychology , medicine , psychiatry , pharmacology , insomnia , environmental health
Autism spectrum disorders ( ASD ) can be conceptualized as a genetic dysfunction that disrupts development and function of brain circuits mediating social cognition and language. At least some forms of ASD may be associated with high level of excitation in neural circuits, and gamma‐aminobutyric acid ( GABA ) has been implicated in its etiology. Single‐nucleotide polymorphisms ( SNP ) located within the GABA receptor ( GABAR ) subunit genes GABRA 1, GABRG 2, GABRB 3, and GABRD were screened. A hundred and thirty‐six A rgentinean ASD patients and 150 controls were studied, and the contribution of the SNPs in the etiology of ASD was evaluated independently and/or through gene–gene interaction using multifactor dimensionality reduction ( MDR ) method. From the 18 SNP studied, 11 were not present in our A rgentinean population (patients and controls) and 1 SNP had minor allele frequency < 0.1%. For the remaining six SNPs , none provided statistical significant association with ASD when considering allelic or genotypic frequencies. Non‐significant association with ASD was found for the haplotype analysis. MDR identified evidence for synergy between markers in GABRB 3 (chromosome 15) and GABRD (chromosome 1), suggesting potential gene–gene interaction across chromosomes associated with increased risk for autism (testing balanced accuracy: 0.6081 and cross‐validation consistency: 10/10, P < 0.001). Considering our A rgentinean ASD sample, it can be inferred that GABRB 3 would be involved in the etiology of autism through interaction with GABRD . These results support the hypothesis that GABAR subunit genes are involved in autism, most likely via complex gene–gene interactions. Autism Res 2014, 7: 162–166. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.