Testing for association based on excess allele sharing in a sample of related cases and controls |
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Authors: | Lambertus Klei Kathyrn Roeder |
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Institution: | (1) Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA;(2) Department of Statistics, Carnegie Mellon University, Pittsburgh, 15213, USA |
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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. |
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Keywords: | |
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