analyses and comparison of imputation-based association methodsimputation-based协会方法的分析和比较.pdfVIP

Analyses and Comparison of Imputation-Based Association Methods 1,2 1,2 2 1,2,3 Yu-Fang Pei , Lei Zhang , Jian Li , Hong-Wen Deng * 1 Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, People’s Republic of China, 2 School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, United States of America, 3 Center of System Biomedical Sciences, Shanghai University of Science and Technology, Shanghai, People’s Republic of China Abstract Genotype imputation methods have become increasingly popular for recovering untyped genotype data. An important application with imputed genotypes is to test genetic association for diseases. Imputation-based association test can provide additional insight beyond what is provided by testing on typed tagging SNPs only. A variety of effective imputation-based association tests have been proposed. However, their performances are affected by a variety of genetic factors, which have not been well studied. In this study, using both simulated and real data sets, we investigated the effects of LD, MAF of untyped causal SNP and imputation accuracy rate on the performances of seven popular imputation-based association methods, including MACH2qtl/dat, SNPTEST, ProbABEL, Beagle, Plink, BIMBAM and SNPMStat. We also aimed to provide a comprehensive comparison among methods. Results show that: 1). imputation-based association tests can boost signals and improve power under medium and high LD levels, with the power improvement increasing with strengthening LD level; 2) the power increases with higher MAF of untyped causal SNPs under medium to high LD le