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Circumventing multiple testing: A multilocus Monte Carlo approach to testing for association

✍ Scribed by Lauren M. McIntyre; Eden R. Martin; Katy L. Simonsen; Norman L. Kaplan


Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
55 KB
Volume
19
Category
Article
ISSN
0741-0395

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✦ Synopsis


Advances in marker technology have made a dense marker map a reality. If each marker is considered separately, and separate tests for association with a disease gene are performed, then multiple testing becomes an issue. A common solution uses a Bonferroni correction to account for multiple tests performed. However, with dense marker maps, neighboring markers are tightly linked and may have associated alleles; thus tests at nearby marker loci may not be independent. When alleles at different marker loci are associated, the Bonferroni correction may lead to a conservative test, and hence a power loss. As an alternative, for tests of association that use family data, we propose a Monte Carlo procedure that provides a global assessment of significance. We examine the case of tightly linked markers with varying amounts of association between them. Using computer simulations, we study a family-based test for association (the transmission/disequilibrium test), and compare its power when either the Bonferroni or Monte Carlo