On Averaging Power for Genetic Association and Linkage Studies

• Activity Number: 94
• Type: Topic Contributed
• Date/Time: Monday, August 8, 2005 : 8:30 AM to 10:20 AM
• Sponsor: Section on Nonparametric Statistics
• Author(s): Jungnam Joo*+ and Gang Zheng and Santhi K. Ganesh and Elizabeth G. Nabel and Nancy L. Geller
• Companies: National Heart, Lung, and Blood Institute and National Heart, Lung, and Blood Institute and National Heart, Lung, and Blood Institute and National Heart, Lung, and Blood Institute and National Heart, Lung, and Blood Institute
• Keywords: Average Power ; Linkage Analysis ; Case-Control Study ; Trend Test

Abstract

In genetic association studies, the power often is calculated using the expected number of individuals calculated from an assumed allele frequency under Hardy-Weinberg equilibrium. Since the allele frequency often is unknown, the number of individuals with each genotype is random. Thus a power calculation assuming a known allele frequency may be incorrect. Ambrosius et al. recently showed the power ignoring this randomness may lead to studies with insufficient power and proposed averaging the power. We extend their method in two directions. First, for testing association in case-control studies, we use the Cochran-Armitage trend test and find the time needed to calculate the averaged power is much reduced compared to the chi-square test studied by Ambrosius et al. Second, we extend the method to linkage analysis, where the number of ibd alleles shared by siblings is random. The distribution of ibd numbers depends on the underlying genetic model rather than the allele frequency. The robust test for linkage analysis also is examined using the averaged powers. We also recommend a sensitivity analysis when the true allele frequency or the number of ibd alleles is unknown.