Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease

作者：Amit V. Khera, Connor A. Emdin, Isabel Drake, Pradeep Natarajan, Alexander G. Bick, Nancy R. Cook, Daniel I. Chasman, Usman Baber, Roxana Mehran, Daniel J. Rader, Valentı́n Fuster, Eric Boerwinkle, Olle Melander, Marju Orho‐Melander, Paul M. Ridker, Sekar Kathiresan · 发表于：New England Journal of Medicine · 年份：2016 · DOI：10.1056/nejmoa1605086 · 被引用次数：1507 · 研究领域：Genetic Associations and Epidemiology、BRCA gene mutations in cancer、Nutrition, Genetics, and Disease

BACKGROUND: Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown. METHODS: Using a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts - 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women's Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) - and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet. RESULTS: The relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low genetic risk (bottom quintile of polygenic scores) (hazard ratio, 1.91; 95% confidence interval [CI], 1.75 to 2.09). A favorable lifestyle (defined as at least three of the four healthy lifestyle factors) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle (defined as no or only one healthy lifestyle factor), regardless of the genetic risk category. Among participants at high genetic risk, a favorable lifestyle was associated wit...