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Association Tests that Accommodate Genotyping Uncertainty * University Press Scholarship Online Oxford Scholarship Online Bayesian Statistics 9 José M. Bernardo, M. J. Bayarri, James O. Berger, A. P. Dawid, David Heckerman, Adrian F. M. Smith, and Mike West Print publication date: 2011 Print ISBN-13: 9780199694587 Published to Oxford Scholarship Online: January 2012 DOI: 10.1093/acprof:oso/9780199694587.001.0001 Association Tests that Accommodate Genotyping Uncertainty * Thomas A. Louis Benilton S. Carvalho M. Daniele Fallin Rafael A. Irizarryi Qing Li Ingo Ruczinski DOI:10.1093/acprof:oso/9780199694587.003.0013 Abstract and Keywords High‐throughput single nucleotide polymorphism (SNP) arrays, typically used in genome‐wide a ociation studies with a trait of interest, provide estimates of genotypes for up to several million loci. Most genotype estimates are very accurate, but genotyping errors do occur and can influence test statistics, p‐values and ranks. Some SNPs are harder to call than others due to probe properties and other technical/biological factors; uncertainties can be a ociated with features of interest. SNP‐ and case‐specific genotype posterior probabilities are available, but they are typically not used or used only informally, for example by setting aside the most uncertain calls. To improve on these approaches we take full advantage of Bayesian structuring and develop an analytic framework that accommodate genotype uncertainties. We show that the power of a score test (and statistical information more generally) is directly a function of the correlation of the genotype probabilities with the true genotypes. We demonstrate that compared to picking a single AA, AB or BB genotype or to setting aside difficult calls, Bayesian structuring can substantially increase statistical information for detecting a true a ociation and for ranking SNPs, whether the ranking be frequentist or optimal Bayes. Thi