A Comparative Study of Power of the Association Tests for Linkage Disequilibrium

• Activity Number: 188
• Type: Contributed
• Date/Time: Monday, August 1, 2011 : 10:30 AM to 12:20 PM
• Sponsor: ENAR
• Author(s): Sayan Dasgupta*+
• Companies: The University of North Carolina at Chapel Hill
• Keywords: TDT ; HHRR ; Hardy Weinberg Equilibrium

Abstract

The transmission disequilibrium test (TDT) was proposed as a family-based association test for the presence of genetic linkage between a genetic marker and a trait. The idea was generated from the proposition that data be gathered in trios of parents plus an affected child. An earlier method (HHRR) used these trios to model the transmitted vs. nontransmitted alleles as units of observation in a haplotype-based haplotype relative risk approach. Considering a recessive disease model in this study, we will use simulation and analytic results to show that: i) The HHRR method is more powerful to detect true association than TDT under the classic situation with 2 alleles and both parents fully observed in case-parent trios assuming that Hardy Weinberg Equilibrium holds. ii) When parental mating choice is not random, so that heterozygous individuals are more likely than expected under HWE in the parental population, the HHRR statistic based on the chi-square(1) null approximation can inflate the Type I error. iii) And lastly we propose an empirical based method that draws on the strengths of both HHRR and TDT, and is more powerful than TDT under modest departures from HWE in parental.