Allelic variants in HTR3C show association with autism

Authors

  • Karola Rehnström,

    Corresponding author
    1. Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland
    2. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
    • Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.
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  • Tero Ylisaukko-oja,

    1. Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland
    2. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
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  • Ilona Nummela,

    1. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
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  • Pekka Ellonen,

    1. Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland
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  • Elli Kempas,

    1. Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland
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  • Raija Vanhala,

    1. Unit of Child Neurology, Hospital for Children and Adolescents, Helsinki, Finland
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  • Lennart von Wendt,

    1. Unit of Child Neurology, Hospital for Children and Adolescents, Helsinki, Finland
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  • Irma Järvelä,

    1. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
    2. Laboratory of Molecular Genetics, Helsinki University Central Hospital (Laboratory Services), Helsinki, Finland
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  • Leena Peltonen

    1. Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland
    2. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
    3. Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts,
    4. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
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  • Please cite this article as follows: Rehnström K, Ylisaukko-oja T, Nummela I, Ellonen P, Kempas E, Vanhala R, von Wendt L, Järvelä I, Peltonen L. 2009. Allelic Variants in HTR3C Show Association With Autism. Am J Med Genet Part B 150B:741–746.

Abstract

Autism spectrum disorders (ASDs) are severe neurodevelopmental disorders with a strong genetic component. Only a few predisposing genes have been identified so far. We have previously performed a genome-wide linkage screen for ASDs in Finnish families where the most significant linkage peak was identified at 3q25-27. Here, 11 positional and functionally relevant candidate genes at 3q25-27 were tested for association with autistic disorder. Genotypes of 125 single nucleotide polymorphisms (SNPs) were determined in 97 families with at least one individual affected with autistic disorder. The most significant association was observed using two non-synonymous SNPs in HTR3C, rs6766410 and rs6807362, both resulting in P = 0.0012 in family-based association analysis. In addition, the haplotype C-C corresponding to amino acids N163-A405 was overtransmitted to affected individuals (P = 0.006). Sequencing revealed no other variants in the coding region or splice sites of HTR3C. Based on the association analysis results in a previously identified linkage region, we propose that HTR3C represents a novel candidate locus for ASDs and should be tested in other populations. © 2008 Wiley-Liss, Inc.

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