title: The Sib TDT adjusted for age of disease onset.
abstract: Since the Sib-TDT (Spielman & Ewens, 1998) ignores age of disease onset, there could be loss of power in detecting linkage. In this article, we propose an adjustment for age of onset using the Cox Proportional Hazard Model (Cox, 1972) with the marker allele as a covariate. The test statistic for linkage is identical to the traditional Sib-TDT. Monte-Carlo simulations are performed under different disease models to assess the increase in power of the age-adjusted Sib-TDT compared to the traditional Sib-TDT. We extend our method to multiallelic markers. An application using data on Alzheimer's Disease is also presented.
authors.affiliation: Applied Statistics Unit, Indian Statistical Institute, Kolkata, India. saurabh@isical.ac.in
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: Theodore
authors.initials: T
authors.lastname: Reich
mesh_terms: D017668:Age of Onset; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D015233:Models, Statistical; D009010:Monte Carlo Method; D009679:Nuclear Family; D019655:Quantitative Trait, Heritable
chemical_list: D005819:Genetic Markers