Family study and segregation analysis of Tourette syndrome: Evidence for a mixed model of inheritance

John T. Walkup, Michele C. Labuda, Harvey S. Singer, Janice Brown, Mark A. Riddle, Orest Hurko

Research output: Contribution to journalArticle

Abstract

To investigate the transmission of Tourette syndrome (TS) and associated disorders within families, complex segregation analysis was performed on family study data obtained from 53 independently ascertained children and adolescents with TS and their 154 first-degree relatives. The results suggest that the susceptibility for TS is conveyed by a major locus in combination with a multifactorial background. Other models of inheritance were definitively rejected, including strictly polygenic models, all single major locus models, and mixed models with dominant and recessive major loci. The frequency of the TS susceptibility allele was estimated to be .01. The major locus accounts for over half of the phenotypic variance for TS, whereas the multifactorial background accounts for ~40% of phenotypic variance. Penetrance estimates suggest that all individuals homozygous for the susceptibility allele at the major locus are affected, whereas only 2.2% of males and 0.3% of females heterozygous at the major locus are affected. Of individuals affected with TS, ~62% are heterozygous and ~38% are homozygous at the major locus. While none of the families had two parents affected with TS, 19% of families had two parents affected with the broader TS phenotype, which includes TS, chronic tic disorder, or obsessive-compulsive disorder.

Original languageEnglish (US)
Pages (from-to)684-693
Number of pages10
JournalAmerican journal of human genetics
Volume59
Issue number3
StatePublished - Aug 27 1996

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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