covariance structure into multivariate GWAS discovery. Genomic SEM is a flexible framework for formally modeling the genetic covariance structure of complex traits using GWAS summary statistics from samples of varying and potentially unknown degrees of overlap, in contrast to existing methods that model phenotypic covariance structure,9 with specific applications,10 using raw data. Moreover, Genomic SEM allows for the specification and comparison of a range of proposed multivariate genetic architectures, which improves upon existing approaches for combining information across genetically correlated traits to aid in discovery.11
