Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA) evaluates pre-specified gene sets for enrichment of modest associations with a complex disease or trait. MAGENTA consists of four main steps: First, DNA variants, e.g. single-nucleotide polymorphisms (SNPs), are mapped onto genes (Figure 1A). Second, each gene is assigned a gene association score that is a function of its regional SNP association p-values (Figure 1B). Third, confounding effects on gene association scores are identified and corrected for, without requiring genotype data (enabling use of meta-analyses or other types of GWA studies where only variant association statistics are available) (Figure 1C). Fourth, a Gene Set Enrichment Analysis (GSEA)-like statistical test is applied to predefined biologically relevant gene sets to determine whether any of the gene sets are enriched for highly ranked gene association scores compared to randomly sampled gene sets of identical size from the genome (Figure 1D). These four steps are described below, and further detailed in the Materials and Methods section.
