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An association analysis of candidate genes on chromosome 15 q11–13 and autism spectrum disorder

Molecular Psychiatry volume 11, pages 709–713 (2006)Cite this article

Autism spectrum disorder (ASD) is conceptualized as a spectrum of related diagnostic categories, comprising subtypes: autism, atypical autism, Asperger's syndrome and other pervasive developmental disorders (ICD-10). Available evidence suggests that several genes contribute to the underlying genetic risk for the development of ASD. However, etiologic and phenotypic heterogeneity impede the discovery of ASD-susceptibility genes. We tested 148 simplex UK families, characterized by both ADI-R and ADOS to have an autism spectrum disorder (ASD), for association with candidate genes, GABRB3, GABRG3, UBE3A and ATP10C, on chromosome 15q11–13. A dense map of single nucleotide polymorphisms (SNPs) that had not been previously parsed in autism, spaced on average by 13 kb, were genotyped across each gene. We found evidence for an association with GABRB3 and ASD. A haplotype analysis of five adjacent SNPs in high linkage disequilibrium (LD) on GABRB3 was significant with a Bonferroni-corrected P-value of 0.00013 for haplotypes of frequency >1% (99.9% of all possible haplotypes covered were represented by seven haplotypes). Further systematic examination of GABRB3 in relation to ASD is required.

Chromosome 15q11–q13 (the Prader-Willi/Angelman Critical Region – PWACR) has been identified as a strong candidate region.1 Evidence for this comes from reports that autistic symptoms are common in patients with chromosomal abnormalities of this region, especially if there is duplications of the maternally derived chromosome 15, as outlined in Bolton et al.2 There have also been a number of suggestive linkage findings.3, 4, 5, 6, 7

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Authors and Affiliations

  1. SGDP, Institute of Psychiatry, London, UK

    S Curran, J Powell, B M Neale, K Dworzynski, T Li, D Murphy & P F Bolton

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Correspondence to S Curran.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Curran, S., Powell, J., Neale, B. et al. An association analysis of candidate genes on chromosome 15 q11–13 and autism spectrum disorder. Mol Psychiatry 11, 709–713 (2006). https://doi.org/10.1038/sj.mp.4001839

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