title: Planning genetic studies on primary adult-onset dystonia: sample size estimates based on examination of first-degree relatives.
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.
authors.affiliation: Department of Neurologic and Psychiatric Sciences, University of Bari, Bari, Italy. gdefazio@neurol.uniba.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Defazio
authors.forename: Davide
authors.initials: D
authors.lastname: Martino
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Aniello
authors.forename: Gianluca
authors.initials: G
authors.lastname: Masi
authors.forename: Angelo
authors.initials: A
authors.lastname: Gigante
authors.forename: Kailash
authors.initials: K
authors.lastname: Bhatia
authors.forename: Paolo
authors.initials: P
authors.lastname: Livrea
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berardelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D020821:Dystonic Disorders / Q000453:epidemiology* / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010808:Physical Examination; D018401:Sample Size; D018709:Statistics, Nonparametric