The derivation of MTAG relies on three important assumptions: (1) Ω is homogeneous across SNPs, (2) sampling variation in Ω^ and ∑^j can be ignored, and (3) the off-diagonal elements of ∑^j (estimated by bivariate LD score regression) accurately capture sample overlap. In light of each assumption, here we probe when and to what extent MTAG’s test statistics for individual-SNP associations may be biased.
