Abstract
Abstract Circulating lipids play a crucial role in the development of coronary artery disease (CAD). However, it is unclear whether the genetic susceptibility to hyperlipidemia may interact with lifestyle factors in CAD risk. Using UK Biobank data from 328,606 participants, we evaluated combined effects of genetic susceptibility to hyperlipidemia and lifestyle factors with risk of CAD. We found that both blood lipid-related polygenic score (PGS) and healthy lifestyle score (HLS) are independently associated with CAD risk, and individuals with the highest-risk lipid-related PGS and the least healthy HLS had the highest CAD risk. This association was stronger in younger (< 60 years, hazard ratio: 4.46, 95% confidence interval: 3.44-5.78) than older adults (2.54, 2.13-3.03). Our study suggests that individuals, particularly younger adults, with higher-risk PGSs of blood lipid traits would benefit more substantially by adherence to a healthy lifestyle than those with lower PGSs.Graphical Abstract