biostudies-literatureBurgess SBritish Heart FoundationMedical Research CouncilNational Institute for Health Research (NIHR)Wellcome Trust658-65https://www.ebi.ac.uk/biostudies/studies/S-EPMC4377079biostudies-literatureUnknown37(7)Genome-wide association studies, which typically report regression coefficients summarizing the associations of many genetic variants with various traits, are potentially a powerful source of data for Mendelian randomization investigations. We demonstrate how such coefficients from multiple variants can be combined in a Mendelian randomization analysis to estimate the causal effect of a risk factor on an outcome. The bias and efficiency of estimates based on summarized data are compared to those based on individual-level data in simulation studies. We investigate the impact of gene-gene interactions, linkage disequilibrium, and 'weak instruments' on these estimates. Both an inverse-variance weighted average of variant-specific associations and a likelihood-based approach for summarized datGenetic epidemiologyMendelian randomization analysis with multiple genetic variants using summarized data.PMC4377079MR/L003120/1NF-SI-0512-10165SP/08/007/23628RG/08/014/24067Thompson SGBurgess SButterworth AfalseMendelian randomization analysis with multiple genetic variants using summarized data.Genome-wide association studies, which typically report regression coefficients summarizing the associations of many genetic variants with various traits, are potentially a powerful source of data for Mendelian randomization investigations. We demonstrate how such coefficients from multiple variants can be combined in a Mendelian randomization analysis to estimate the causal effect of a risk factor on an outcome. The bias and efficiency of estimates based on summarized data are compared to those based on individual-level data in simulation studies. We investigate the impact of gene-gene interactions, linkage disequilibrium, and 'weak instruments' on these estimates. Both an inverse-variance weighted average of variant-specific associations and a likelihood-based approach for summarized dat2013-01-01T00:00:00Z2013 Nov2025-04-19T00:45:56.595Z2019-03-27T01:48:56ZS-EPMC43770792411480210.1002/gepi.21758