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  • Original Research Article
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Association between a GABRB3 polymorphism and autism

Abstract

Autistic disorder (OMIM 209850) is a disease with a significant genetic component of a complex nature.1 Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (15q11–13) have been described in several individuals with autism.1 For this reason, markers across this region have been screened for evidence of linkage and association, and a marker (155CA-2) in the γ-aminobutyric acid type-A receptor β3 subunit gene (GABRB3) has been associated in one study2 but not others.3–5 We completed an association analysis with 155CA-2 using the transmission disequilibrium test (TDT) in a set of 80 autism families (59 multiplex and 21 trios). We also used four additional markers (69CA, 155CA-1, 85CA, and A55CA-1) localized within 150 kb of 155CA-2. The use of multi-allelic TDT (MTDT) (P < 0.002), as well as the TDT (P < 0.004), demonstrated an association between autistic disorder and 155CA-2 in these families. Meiotic segregation distortion could be excluded as a possible cause for these results since no disequilibrium was observed in unaffected siblings. These findings support a role for genetic variants within the GABA receptor gene complex in 15q11–13 in autistic disorder.

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Acknowledgements

These studies were supported by grants from the Seaver Autism Research Center and Cure Autism Now. We acknowledge support from Cure Autism Now and the Autism Genetic Resource Exchange (AGRE27) and we gratefully acknowledge the resources provided by the AGRE consortium27 and the participating AGRE families.

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Correspondence to J D Buxbaum.

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Buxbaum, J., Silverman, J., Smith, C. et al. Association between a GABRB3 polymorphism and autism. Mol Psychiatry 7, 311–316 (2002). https://doi.org/10.1038/sj.mp.4001011

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