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Power of association and linkage tests when the disease alleles are unobserved.
Authors:I P Tu and A S Whittemore
Affiliation:Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA.
Abstract:Genomewide association studies have been advocated as a promising alternative to genomewide linkage scans for detection of small-effect genes in complex diseases. Comparisons of power and sample size between the two strategies have shown considerable advantages for the association studies. These comparisons assume that the set of markers includes the exact disease-related polymorphism. A concern, however, is that the power of an association study decreases when this is not the case, because of discrepant allele frequencies and less-than-maximum disequilibrium between the disease-related polymorphism and its nearest marker. Here, we quantify this concern by comparing the sample sizes needed by the two strategies when the markers exclude the disease-related polymorphism. For affected sib pairs and their parents, we found that incomplete disequilibrium and differing allele frequencies can have substantial negative impact on the power of association studies, resulting, in some circumstances, in little gain and even in loss of power, compared with linkage analysis. We provide some guidelines for choosing between strategies, for the detection of genes for complex diseases.
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