the impact of imputation on meta-analysis of genome-wide association studies归责的影响全基因组关联研究的荟萃分析.pdfVIP

The Impact of Imputation on Meta-Analysis of Genome-Wide Association Studies 1 2 1,3 1,3,4 Jian Li , Yan-fang Guo , Yufang Pei , Hong-Wen Deng * 1 School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America, 2 School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of China, 3 Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China, 4 Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, People’s Republic of China Abstract Genotype imputation is often used in the meta-analysis of genome-wide association studies (GWAS), for combining data from different studies and/or genotyping platforms, in order to improve the ability for detecting disease variants with small to moderate effects. However, how genotype imputation affects the performance of the meta-analysis of GWAS is largely unknown. In this study, we investigated the effects of genotype imputation on the performance of meta-analysis through simulations based on empirical data from the Framingham Heart Study. We found that when fix-effects models were used, considerable between-study heterogeneity was detected when causal variants were typed in only some but not all individual studies, resulting in up to ,25% reduction of detection power. For certain situations, the power of the meta- analysis can be even less than that of individual studies. Additional analyses showed that the detection power was slightly improved when betwe