APOC3 and heart disorder: Indeed, heterozygous carriers of loss-of-function mutations in APOC3 have a 46% lower risk of coronary heart disease5 and 36% lower risk of ischaemic heart disease.6 Additionally, our previous Mendelian randomization (MR) analysis showed that genetically predicted lower plasma levels of the APOC3 protein are associated with a significantly reduced risk of coronary artery disease (CAD).7,8 However, our understanding of how APOC3 levels could influence CVD is incomplete.