Using SCZ GWAS as a representative example, we next compared H-MAGMA with eQTL-based gene annotation tools, coloc and TWAS (Methods). Coloc tests whether GWAS SNPs and eQTLs in a certain GWS locus share the same causal variant9, whereas TWAS imputes the genotype-expression relationship based on the eQTL association statistics and derives expression-trait associations by correlating the imputed gene expression to the trait11. We found that a significant proportion of genes identified by eQTL-based gene mapping were also detected by H-MAGMA (Fig. 1d, 74.9% of coloc genes, Fisher’s exact test, OR=4.34, 95% CI=3.22–5.90, P=1.76x10–26; 72.6% of TWAS genes, Fisher’s exact test, OR=12.14, 95% CI=10.20–14.49, P=3.94x10–206). H-MAGMA detected a much larger number of genes to be associated with SCZ, which explained a significant proportion of heritability (4.7% of SNPs explained 38.93% of heritability, Enrichment = 8.23, Enrichment P= 7.17x10–53, Methods).
