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 journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)861-867
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume141
Issue number8
DOIs
StatePublished - Dec 5 2006
Externally publishedYes

Fingerprint

Autistic Disorder
Compulsive Behavior
Obsessive Behavior
Single Nucleotide Polymorphism
Genes
Serotonin
Endophenotypes
Haplotypes
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Ramoz, N., Cai, G., Reichert, J. G., Corwin, T. E., Kryzak, L. A., Smith, C. J., ... Buxbaum, J. D. (2006). Family-based association study of TPH1 and TPH2 polymorphisms in autism. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 141(8), 861-867. https://doi.org/10.1002/ajmg.b.30356

Family-based association study of TPH1 and TPH2 polymorphisms in autism. / Ramoz, Nicolas; Cai, Guiqing; Reichert, Jennifer G.; Corwin, Thomas E.; Kryzak, Lauren A.; Smith, Christopher J.; Silverman, Jeremy M.; Hollander, Eric; Buxbaum, Joseph D.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 141, No. 8, 05.12.2006, p. 861-867.

Research output: Contribution to journalArticle

Ramoz, N, Cai, G, Reichert, JG, Corwin, TE, Kryzak, LA, Smith, CJ, Silverman, JM, Hollander, E & Buxbaum, JD 2006, 'Family-based association study of TPH1 and TPH2 polymorphisms in autism', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 141, no. 8, pp. 861-867. https://doi.org/10.1002/ajmg.b.30356
Ramoz, Nicolas ; Cai, Guiqing ; Reichert, Jennifer G. ; Corwin, Thomas E. ; Kryzak, Lauren A. ; Smith, Christopher J. ; Silverman, Jeremy M. ; Hollander, Eric ; Buxbaum, Joseph D. / Family-based association study of TPH1 and TPH2 polymorphisms in autism. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2006 ; Vol. 141, No. 8. pp. 861-867.
@article{5703cbcdc5cd4db9900a7ea7f0b502ec,
title = "Family-based association study of TPH1 and TPH2 polymorphisms in autism",
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.",
keywords = "Autistic disorder, Obsessive-compulsive behaviors, Serotonin, Transmission, Tryptophan-hydroxylase",
author = "Nicolas Ramoz and Guiqing Cai and Reichert, {Jennifer G.} and Corwin, {Thomas E.} and Kryzak, {Lauren A.} and Smith, {Christopher J.} and Silverman, {Jeremy M.} and Eric Hollander and Buxbaum, {Joseph D.}",
year = "2006",
month = "12",
day = "5",
doi = "10.1002/ajmg.b.30356",
language = "English (US)",
volume = "141",
pages = "861--867",
journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Family-based association study of TPH1 and TPH2 polymorphisms in autism

AU - Ramoz, Nicolas

AU - Cai, Guiqing

AU - Reichert, Jennifer G.

AU - Corwin, Thomas E.

AU - Kryzak, Lauren A.

AU - Smith, Christopher J.

AU - Silverman, Jeremy M.

AU - Hollander, Eric

AU - Buxbaum, Joseph D.

PY - 2006/12/5

Y1 - 2006/12/5

N2 - 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.

AB - 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.

KW - Autistic disorder

KW - Obsessive-compulsive behaviors

KW - Serotonin

KW - Transmission

KW - Tryptophan-hydroxylase

UR - http://www.scopus.com/inward/record.url?scp=33845393999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845393999&partnerID=8YFLogxK

U2 - 10.1002/ajmg.b.30356

DO - 10.1002/ajmg.b.30356

M3 - Article

VL - 141

SP - 861

EP - 867

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 8

ER -