Transmission Disequilibrium Test Power and Sample Size in the Presence of Locus Heterogeneity

Chen Chuanwen, Yang Guang, Buyske Steven, Matise Tara, Finch Stephen J and Gordon Derek
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Chen Chuanwen: Rutgers University
Yang Guang: Rutgers University
Buyske Steven: Rutgers University
Matise Tara: Rutgers University
Finch Stephen J: Stony Brook University
Gordon Derek: Rutgers University

Statistical Applications in Genetics and Molecular Biology, 2009, vol. 8, issue 1, 18

Abstract: Locus heterogeneity is one of the most important issues in gene mapping and can cause significant reductions in statistical power for gene mapping, yet no research to date has provided power and sample size calculations for family-based association methods in the presence of locus heterogeneity. The purpose of this research is three-fold: (i) to provide an analytic solution to the incorporation of locus heterogeneity into power and sample size calculations for the TDT statistic; (ii) to verify our analytic solution with simulations; and (iii) to study how different factors affect sample size requirement for the TDT in the presence of locus heterogeneity.The detection of association in the presence of locus heterogeneity requires a greater sample size than in its absence. This increase is independent of the prevalence of the disease. In addition, as the proportion of families unlinked to the disease locus increases, the sample size necessary to maintain constant power increases. Finally, as the effect size of the disease locus increases, the sample size necessary to detect association decreases in the presence of locus heterogeneity. We provide freely available software that can perform these calculations.

Keywords: mixture; noncentrality parameter; family-based association (search for similar items in EconPapers)
Date: 2009
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DOI: 10.2202/1544-6115.1501

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