Planning genetic studies on primary adult-onset dystonia: Sample size estimates based on examination of first-degree relatives
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- 作者：Giovanni Defazio ; Davide Martino ; Maria Stella Aniello ; Gianluca Masi ; Angelo Gigante ; Kailash Bhatia ; Paolo Livrea ; Alfredo Berardelli
- 关键词：Primary dystonia ; Adult-onset ; Genetics ; Sample size ; Statistical design
- 刊名：Journal of the Neurological Sciences
- 出版年：2006
- 出版时间：21 December 2006
- 年：2006
- 卷：251
- 期：1-2
- 页码：29-34
- 全文大小：209 K
文摘
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.