Planning genetic studies on primary adult-onset dystonia: Sample size estimates based on examination of first-degree relatives

Giovanni Defazio, Davide Martino, Maria Stella Aniello, Gianluca Masi, Angelo Gigante, Kailash Bhatia, Paolo Livrea, Alfredo Berardelli

Research output: Contribution to journalArticle


Primary adult-onset dystonia is thought to be partly genetic, but families large enough for a genome wide search are difficult to find. We examined the first-degree relatives of 76 primary adult-onset dystonia patients to assess the feasibility of model-free nonparametric methods that allow either screening of candidate loci (case-control design, transmission disequilibrium test [TDT], and sibling-TDT [S-TDT]) or identification of novel genes (affected sib-pair [ASP] method). Among the examined relatives, 1/34 parents, 13/149 siblings and 10/125 offspring were affected by adult-onset dystonia. The predicted sample sizes to detect a gene conferring an Odds ratio of 3.0 were 99 for case-control and TDT methodology, 148 for S-TDT, and 107 to 173 for an ASP study assuming three major loci. Based on our family structure, TDT, S-TDT, and ASP methods would required screening of about 220, 700, and 580 to 939 probands respectively. Analysing subpopulations with different types of dystonia, TDT required fewer probands with cervical/hand dystonia, S-TDT needed fewer probands with cranial dystonia. These sample size estimates suggest that the S-TDT may be feasible, whereas collection of cases for both TDT and ASP approaches would represent a major collaborative challenge.

Original languageEnglish
Pages (from-to)29-34
Number of pages6
JournalJournal of the Neurological Sciences
Issue number1-2
Publication statusPublished - Dec 21 2006



  • Adult-onset
  • Genetics
  • Primary dystonia
  • Sample size
  • Statistical design

ASJC Scopus subject areas

  • Ageing
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this