While observational studies consistently report a protective association of high blood HDL‐C levels with lower CHD risk, previous MR studies show that HDL‐C is not a causal risk factor for CHD.48, 57 Furthermore, a recent study has reported that a loss‐of‐function variant in scavenger receptor BI (SRB1) raises HDL‐C and increases CHD risk.58 Further studies are warranted to understand potential biological mechanisms of a PAI‐1 effect on HDL‐C and whether HDL‐C is an intermediary between the PAI‐1 and CHD associations. This evidence concerns the gene SERPINE1 and coronary artery disorder.