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

Nicolas Ramoz, Guiqing Cai, Jennifer G. Reichert, Thomas E. Corwin, Lauren A. Kryzak, Christopher J. Smith, Jeremy M. Silverman, Eric Hollander, Joseph D. Buxbaum

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)861-867
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number8
StatePublished - Dec 5 2006
Externally publishedYes


  • Autistic disorder
  • Obsessive-compulsive behaviors
  • Serotonin
  • Transmission
  • Tryptophan-hydroxylase

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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