Conversely, two loci had significant buffering of disease risk alleles by reaction fluxes in MI and not in CAD: effect sizes of 15 risk alleles mapped to the PDE5A/MAD2L1 locus, and 13 risk alleles mapped to the MAP1S/FCHO1 locus were buffered by the flux of orotate phosphoribosyltransferase in heart and uracil transport in skeletal muscle, respectively (Fig. EV4). Here, MAD2L1 is linked to coronary artery disorder.