Table 3

GSEA of T2D associations in individual drug class target sets before and after removing genes in established T2D loci

All genes analyzedExcluding genes in LD to validated T2D SNPs
Antidiabetes drug target gene setNumber of genes analyzed*Nominal MAGENTA enrichment P valueEnrichment fold (OBS/EXP)Excess number of genes above enrichment cutoff (OBS − EXP)Number of genes analyzed*Nominal MAGENTA enrichment P valueEnrichment fold (OBS/EXP)Excess number of genes above enrichment cutoff (OBS − EXP)Genes in LD to validated T2D SNPs
All nine classes of drugs921.7 × 10−51.818874 × 10−41.715PPARG, IRS1, KCNJ11/ABCC8, IDE, GIPR
Insulin160.0012.56158 × 10−42.56IRS1
TZDs380.021.66360.011.76PPARG, IRS1
DPP4 inhibitors180.151.42170.221.52
GLP-1 receptor agonists170.381.31170.491.31
  • EXP, expected; OBS, observed.

  • *Number of genes analyzed after excluding genes in HLA region (one gene) and genes on sex chromosomes (three genes) and correcting for physical clustering of subsets of genes within a given gene set along the genome (six genes).

  • †Genes were mapped onto 55 established T2D SNPs using the larger of two boundaries around each SNP: ±100 kb or LD r2 > 0.5 (see research design and methods and Supplementary Table 3).

  • ‡The gene P value of IRS1 did not pass the enrichment cutoff because the validated T2D GWAS SNP near IRS1 lies farther away than the gene boundaries used in the MAGENTA analysis.