Fig. 3: Drug-target MR results assessing proxying metformin and other antidiabetics targets with mvAge.
Data presented are MR effect estimates (betas) for the IVW MR method (the primary MR method) and the corresponding 95% confidence intervals (CIs) aligned to proxy the pharmacological effect of metformin and antidiabetic genes (HbA1c GWAS n = 344,182) (1 s.d. lowering of HbA1c levels) on mvAge (n = 1,958,774). The vertical line in the center of the forest plots is 0, corresponding to no change in the IVW estimate of the drug targets on mvAge. Full results are presented in Supplementary Tables 15 and 16. Metformin results plotted show the MR estimates for the primary metformin instrument (top row), which comprised variants within genes for five metformin targets (AMPK, GSD15, MCI, MG3 and GLP1), for the estimates of the alternative metformin instruments used as sensitivity analyses, and the metformin targets separated into individual instruments. See Methods and Supplementary Methods sections for additional details. For the analyses of the antidiabetic classes not including the metformin targets, the * indicates that the thiazolidinedione MR estimate surpasses the Bonferroni-adjusted P-value threshold = 0.002, corrected for the 25 antidiabetic, lipid-modulating and antihypertensive drug targets compared. P values are derived from two-sided Wald tests. Gene names for the nearest mapped genes are italicized.
