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Am. J. Hum. Genet. 74:432443, 2004 Increasing the Power and Efficiency of Disease-Marker Case-Control

Summary: Am. J. Hum. Genet. 74:432­443, 2004
Increasing the Power and Efficiency of Disease-Marker Case-Control
Association Studies through Use of Allele-Sharing Information
Tasha E. Fingerlin,1,2,3
Michael Boehnke,2,3
and Gonc¸alo R. Abecasis2,3
Departments of 1
Epidemiology and 2
Biostatistics, School of Public Health, and 3
Center for Statistical Genetics, University of Michigan,
Ann Arbor
Case-control disease-marker association studies are often used in the search for variants that predispose to complex
diseases. One approach to increasing the power of these studies is to enrich the case sample for individuals likely
to be affected because of genetic factors. In this article, we compare three case-selection strategies that use allele-
sharing information with the standard strategy that selects a single individual from each family at random. In
affected sibship samples, we show that, by carefully selecting sibships and/or individuals on the basis of allele
sharing, we can increase the frequency of disease-associated alleles in the case sample. When these cases are compared
with unrelated controls, the difference in the frequency of the disease-associated allele is therefore also increased.
We find that, by choosing the affected sib who shows the most evidence for pairwise allele sharing with the other


Source: Abecasis, Goncalo - Department of Biostatistics, University of Michigan


Collections: Biology and Medicine; Mathematics