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Testing for Association based on Excess Allele Sharing in a Simple of related Cases and Controls



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Hum Genet 2007 121 549 557 DOI 10 1007 s00439 007 0345 z ORIGINAL INVESTIGATION Testing for association based on excess allele sharing in a sample of related cases and controls Lambertus Klei Kathyrn Roeder Received 21 November 2006 Accepted 12 February 2007 Published online 7 March 2007 Springer Verlag 2007 Abstract Samples consisting of a mix of unrelated cases and controls small pedigrees and much larger pedigrees present a unique challenge for association studies Few methods are available for efficient analysis of such a broad spectrum of data structures In this paper we introduce a new matching statistic that is well suited to complex data structures and compare it with frequency based methods available in the literature To investigate and compare the power of these methods we simulate datasets based on complex pedigrees We examine the influence of various levels of linkage disequilibrium LD of the disease allele with a marker allele or equivalently a haplotype For low frequency marker alleles haplotypes frequency based statistics are more powerful in detecting association In contrast for high frequency marker alleles the matching statistic has greater power The highest power for frequency based statistics occurs when the disease allele frequency closely matches the frequency of the linked marker allele In contrast maximum power of the matching statistic always occurs for intermediate marker allele frequency regardless of the disease allele frequency Moreover the matching and frequency based statistics exhibit little correlation We conclude that these two approaches can be viewed as complementary in finding possible association between a disease and a marker for many different situations L Klei Western Psychiatric Institute and Clinic University of Pittsburgh Medical Center Pittsburgh PA 15213 USA K Roeder Department of Statistics Carnegie Mellon University Pittsburgh 15213 USA e mail roeder stat cmu edu Introduction Subjects originally recruited for linkage



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