biostudies-literatureZhang ZNCI NIH HHSNational Institutes of HealthCancer Prevention Research Institute of Texas146-155https://www.ebi.ac.uk/biostudies/studies/S-EPMC8682785biostudies-literatureUnknown31(1)Genotype imputation is widely used in genetic studies to boost the power of GWAS, to combine multiple studies for meta-analysis and to perform fine mapping. With advances of imputation tools and large reference panels, genotype imputation has become mature and accurate. However, the uncertain nature of imputed genotypes can cause bias in the downstream analysis. Many studies have compared the performance of popular imputation approaches, but few investigated bias characteristics of downstream association analyses. Herein, we showed that the imputation accuracy is diminished if the real genotypes contain minor alleles. Although these genotypes are less common, which is particularly true for loci with low minor allele frequency, a large discordance between imputed and observed genotypes signHuman molecular geneticsFalse positive findings during genome-wide association studies with imputation: influence of allele frequency and imputation accuracy.PMC8682785R01CA242218RR170048U19CA203654R03 CA256222R01 CA242218U19 CA203654Amos CIZhang ZXiao XZhou WZhu DfalseFalse positive findings during genome-wide association studies with imputation: influence of allele frequency and imputation accuracy.Genotype imputation is widely used in genetic studies to boost the power of GWAS, to combine multiple studies for meta-analysis and to perform fine mapping. With advances of imputation tools and large reference panels, genotype imputation has become mature and accurate. However, the uncertain nature of imputed genotypes can cause bias in the downstream analysis. Many studies have compared the performance of popular imputation approaches, but few investigated bias characteristics of downstream association analyses. Herein, we showed that the imputation accuracy is diminished if the real genotypes contain minor alleles. Although these genotypes are less common, which is particularly true for loci with low minor allele frequency, a large discordance between imputed and observed genotypes sign2021-01-01T00:00:00Z2021 Dec2025-04-05T16:10:47.14Z2025-04-05T16:10:47.14ZS-EPMC86827853436884710.1093/hmg/ddab203