A rare, high-impact genetic variant associated with a substantially lower plasma triglyceride level is reported online in Nature Communications this week. Plasma triglyceride level is a well-established risk factor for cardiovascular disease. This low-frequency, high-impact variant is one of the first of its kind to be identified using whole-genome sequencing of large populations of individuals.
Although genetic factors are known to play an important role in determining an individual’s cardiovascular disease risk, most factors identified so far are relatively common and account for only a small amount of the variation in the risk of developing the disease. It is hoped that whole-genome, large population studies will identify less common variants that have a bigger effect on disease risk.
Nicole Soranzo and colleagues at the UK10K Consortium find that around 0.25% of the UK population - approximately 160,000 people - are likely to carry a version of the APOC3 gene, which they find is associated with lower levels of plasma triglyceride. They also report that the variant is associated with lower levels of very-low-density lipoprotein (so-called “bad cholesterol”), and higher levels of high-density lipoprotein (so-called “good cholesterol”). These changes would be expected to result in a lower overall risk of cardiovascular disease.