Table 6

Testing for potential nonglycemic effects of TZDs or other antidiabetes drug classes on global lipid plasma levels through GSEA of genetic associations

LDL-C GWAS meta-analysisTriglyceride GWAS meta-analysisHDL-C GWAS meta-analysis
Antidiabetes drug target gene setNumber of genes analyzed*Nominal MAGENTA enrichment P valueExcess number of genes above enrichment cutoffNominal MAGENTA enrichment P valueExcess number of genes above enrichment cutoffNominal MAGENTA enrichmentP valueExcess number of genes above enrichment cutoffAntidiabetes drug target genes in LD to validated lipid SNPs
TZDs380.000790.0640.351APOA1 (TG, HDL-C, LDL-C), IRS1 (HDL-C, TG), SCARB1 (HDL-C)
All nine classes of drugs94–950.01100.0380.223APOA1 (TG, HDL-C, LDL-C), IRS1 (HDL-C, TG), SCARB1 (HDL-C)
Insulin160.1920.3510.351IRS1 (HDL-C, TG)
GLP-1 receptor agonists170.6500.1030.240
DPP4 inhibitors18–200.9100.6700.880
  • TG, triglyceride.

  • *Number of genes analyzed after excluding genes in HLA region and genes on sex chromosomes and correcting for physical clustering along the genome of genes within a given gene set. The number varies a bit between GWAS meta-analyses due to slight differences in SNP coverage between traits. Because of the physical proximity of APOC3 and APOA1, these genes were collapsed into one effective gene in the enrichment analysis (choosing the more significant gene P value) to prevent inflation of the gene set enrichment P value.

  • †Passes Bonferroni correction, P < 0.003.

  • ‡Based on 95 loci associated with global lipid traits in (33).