Family-based association study of TPH1 and TPH2 polymorphisms in autism

Authors

  • Nicolas Ramoz,

    1. Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, New York
    2. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
    3. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York
    Current affiliation:
    1. INSERM U675, Paris, France.
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  • Guiqing Cai,

    1. Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, New York
    2. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
    3. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York
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  • Jennifer G. Reichert,

    1. Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, New York
    2. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
    3. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York
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  • Thomas E. Corwin,

    1. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
    2. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York
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  • Lauren A. Kryzak,

    1. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
    2. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York
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  • Christopher J. Smith,

    1. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
    2. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York
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  • Jeremy M. Silverman,

    1. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
    2. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York
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  • Eric Hollander,

    1. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
    2. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York
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  • Joseph D. Buxbaum

    Corresponding author
    1. Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, New York
    2. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
    3. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York
    4. Departments of Neuroscience, and Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York
    • Laboratory of Molecular Neuropsychiatry, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1668, New York 10029, NY.
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  • Nicolas Ramoz and Guiqing Cai contributed equally to the work.

  • Please cite this article as follows: Ramoz N, Cai G, Reichert JG, Corwin TE, Kryzak L, Smith CJ, Silverman JM, Hollander E, Buxbaum JD. 2006. Family-Based Association Study of TPH1 and TPH2 Polymorphisms in Autism. Am J Med Genet Part B 141B:861–867.

Abstract

The TPH1 and TPH2 genes encode the rate-limiting enzymes that control serotonin biosynthesis, and serotonin is clearly altered in autism. In the current study, eight SNPs in the TPH1 gene region and eight SNPs within the TPH2 gene were examined by family-based association tests in a large cohort of 352 families with autism and in clinically defined subsets of these families with either severe obsessive-compulsive behaviors (sOCB) or self-stimulatory behaviors (SSB). We found no evidence for association between autism and single SNPs or haplotypes of the TPH1 and TPH2 genes in the cohort of all families or in the sOCB and SSB subsets. In particular, we failed to replicate the association between autism and variants of the TPH2 gene, rs4341581 (TRANSMIT P = 1; PDT P = 0.323; FBAT P = 0.446) and rs11179000 (TRANSMIT P = 0.174; PDT P = 0.293; FBAT P = 0.374). Furthermore, no evidence for linkage was observed between autism and SNPs in the TPH1 and TPH2 genes (although linkage at the TPH2 locus was observed in the SSB subset). Thus, it appears unlikely that the TPH1 and TPH2 genes play a significant role in the susceptibility to autism or to autism endophenotypes including sOCB and SSB. © 2006 Wiley-Liss, Inc.

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