title: Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies.
abstract: BACKGROUND
  Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait.
  
  
  RESULTS
  We examined 2 dichotomous phenotypes of ideal CV health-clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical+behavioral (clinical plus: not a current smoker, body mass index <25 kg/m(2))-among white participants aged 50±5 years. We performed a meta-analysis of 4 genome-wide association studies (total n=11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P<2.0 × 10(-9)). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol.
  
  
  CONCLUSIONS
  A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Electronic address: Norrina-allen@northwestern.edu.
authors.forename: Norrina B
authors.initials: NB
authors.lastname: Allen
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Donald
authors.initials: D
authors.lastname: Lloyd-Jones
authors.affiliation: Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA; NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Laura
authors.initials: L
authors.lastname: Rasmussen-Torvik
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX.
authors.forename: Alanna C
authors.initials: AC
authors.lastname: Morrison
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Baldridge
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA; NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.affiliation: Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA; NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.affiliation: Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, QC, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Thanassoulis
authors.affiliation: Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, QC, Canada.
authors.forename: Line
authors.initials: L
authors.lastname: Dufresne
authors.affiliation: University of Illinois, Chicago, IL.
authors.forename: Martha
authors.initials: M
authors.lastname: Daviglus
authors.affiliation: Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA; NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Johnson
authors.affiliation: National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD.
authors.forename: Jared
authors.initials: J
authors.lastname: Reis
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA.
authors.forename: Jerome
authors.initials: J
authors.lastname: Rotter
authors.affiliation: Department of Medicine, Columbia University, New York, NY.
authors.forename: Walter
authors.initials: W
authors.lastname: Palmas
authors.affiliation: Division of Preventive Medicine, University of California, San Diego, CA.
authors.forename: Mathew
authors.initials: M
authors.lastname: Allison
authors.affiliation: University of Minnesota, Minneapolis, MN.
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.affiliation: Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA; NHLBI's Framingham Heart Study, Framingham, MA; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
mesh_terms: D053302:Apolipoprotein C-I / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D065840:Protective Factors
chemical_list: C505803:APOC1 protein, human; D053302:Apolipoprotein C-I