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

6 Citations (Scopus)

Abstract

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
Volume251
Issue number1-2
DOIs
Publication statusPublished - Dec 21 2006

Fingerprint

Dystonic Disorders
Sample Size
Siblings
Dystonia
Torticollis
Internal-External Control
Genes
Hand
Odds Ratio
Genome

Keywords

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

ASJC Scopus subject areas

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

Cite this

Planning genetic studies on primary adult-onset dystonia : Sample size estimates based on examination of first-degree relatives. / Defazio, Giovanni; Martino, Davide; Aniello, Maria Stella; Masi, Gianluca; Gigante, Angelo; Bhatia, Kailash; Livrea, Paolo; Berardelli, Alfredo.

In: Journal of the Neurological Sciences, Vol. 251, No. 1-2, 21.12.2006, p. 29-34.

Research output: Contribution to journalArticle

Defazio, Giovanni ; Martino, Davide ; Aniello, Maria Stella ; Masi, Gianluca ; Gigante, Angelo ; Bhatia, Kailash ; Livrea, Paolo ; Berardelli, Alfredo. / Planning genetic studies on primary adult-onset dystonia : Sample size estimates based on examination of first-degree relatives. In: Journal of the Neurological Sciences. 2006 ; Vol. 251, No. 1-2. pp. 29-34.
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