Large-scale exome-sequencing identified rare variants which might explain part of the missing heritability for coronary artery disease

In close collaboration with several national and international colleagues members of the IIEG conducted large-scale exome-sequencing in thousands of patients with coronary artery disease and healthy controls. Three papers have been published in the last three months in the prestigious journals NEJM and Nature.

First, we reported that rare mutations disrupting APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease.

Second, we described naturally occurring rare loss-of-function mutations in NPC1L1, a drug target for lowering LDL-cholesterol, which were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease. Interestingly, human mutations that inactivate a gene encoding a drug target can mimic the action of an inhibitory drug and thus can be used to infer potential effects of that drug.

Third, we identified rare mutations in APOA5 gene which confer a more than two-fold risk for myocardial infarction.

Scroll to Top