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Effect of linkage disequilibrium on the identification of functional variants

โœ Scribed by Alun Thomas; Haley J. Abel; Yanming Di; Laura L. Faye; Jing Jin; Jin Liu; Zheyan Wu; Andrew D. Paterson


Book ID
102226798
Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
89 KB
Volume
35
Category
Article
ISSN
0741-0395

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โœฆ Synopsis


Abstract

We summarize the contributions of Group 9 of Genetic Analysis Workshop 17. This group addressed the problems of linkage disequilibrium and other longer range forms of allelic association when evaluating the effects of genotypes on phenotypes. Issues raised by longโ€range associations, whether a result of selection, stratification, possible technical errors, or chance, were less expected but proved to be important. Most contributors focused on regression methods of various types to illustrate problematic issues or to develop adaptations for dealing with highโ€density genotype assays. Study design was also considered, as was graphical modeling. Although no method emerged as uniformly successful, most succeeded in reducing falseโ€positive results either by considering clusters of loci within genes or by applying smoothing metrics that required results from adjacent loci to be similar. Two unexpected results that questioned our assumptions of what is required to model linkage disequilibrium were observed. The first was that correlations between loci separated by large genetic distances can greatly inflate singleโ€locus test statistics, and, whether the result of selection, stratification, possible technical errors, or chance, these correlations seem overabundant. The second unexpected result was that applying principal components analysis to genomeโ€wide genotype data can apparently control not only for population structure but also for linkage disequilibrium. Genet. Epidemiol. 35:S115โ€“S119, 2011. ยฉ 2011 Wiley Periodicals, Inc.


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