Correlation between GWAS estimates can arise for two reasons. First, the traits may be genetically correlated, in which case the true effects of the SNPs are correlated across traits. Second, the estimation error of the SNPs’ effects may be correlated across traits. Such correlation will occur if (a) the phenotypic correlations are non-zero and there is sample overlap across traits, or if (b) biases in the SNP-effect estimates (e.g., population stratification or cryptic relatedness) have correlated effects across traits. MTAG boosts statistical power by incorporating information about these two sources of correlation.
