title: The impact of imputation on meta-analysis of genome-wide association studies.
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 between-study heterogeneity was partially controlled through the random-effects model, relative to that of the fixed-effects model. Our study may aid in the planning, data analysis, and interpretation of GWAS meta-analysis results when genotype imputation is necessary.
authors.affiliation: School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Yufang
authors.initials: Y
authors.lastname: Pei
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics*; D003198:Computer Simulation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015201:Meta-Analysis as Topic; D008957:Models, Genetic; D015233:Models, Statistical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*