title: Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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 with a 46% lower relative risk of coronary events than an unfavorable lifestyle (hazard ratio, 0.54; 95% CI, 0.47 to 0.63). This finding corresponded to a reduction in the standardized 10-year incidence of coronary events from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS. In the BioImage Study, a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category.
  
  
  
  Across four studies involving 55,685 participants, genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavorable lifestyle. (Funded by the National Institutes of Health and others.).
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Amit V
authors.initials: AV
authors.lastname: Khera
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Connor A
authors.initials: CA
authors.lastname: Emdin
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Isabel
authors.initials: I
authors.lastname: Drake
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Pradeep
authors.initials: P
authors.lastname: Natarajan
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Bick
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Usman
authors.initials: U
authors.lastname: Baber
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) - all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.).
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D000070497:Healthy Lifestyle; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D010349:Patient Compliance; D011110:Polymorphism, Genetic; D012306:Risk