title: Risk scores of common genetic variants for lipid levels influence atherosclerosis and incident coronary heart disease.
abstract: OBJECTIVE
  Circulating levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides are recognized risk factors for cardiovascular disease. We tested the hypothesis that the cumulative effects of common genetic variants for lipids are collectively associated with subclinical atherosclerosis and incident coronary heart disease.
  
  
  RESULTS
  Participants were drawn from the Erasmus Rucphen Family Study (n=2269) and the Rotterdam Study (n=8130). Linear regression and Cox proportional hazards models were applied to assess the influence of 4 risk scores derived from common genetic variants for lipids (total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglycerides) on carotid plaque, intima-media thickness, incident myocardial infarction, and coronary heart disease. Adjusted for age and sex, all 4 risk scores were associated with carotid plaque. This relationship was the strongest for the LDL-C score, which increased plaque score by 0.102 per SD increase in genetic risk score (P=3.2 × 10(-8)). The LDL-C score was also nominally associated with intima-media thickness, which increased 0.006 mm per SD increase in score (P=0.05). Both the total cholesterol and LDL-C scores were associated with incident myocardial infarction and coronary heart disease with hazard ratios between 1.10 and 1.13 per SD increase in score. Inclusion of additional risk factors as covariates minimally affected these results.
  
  
  CONCLUSIONS
  Common genetic variants with small effects on lipid levels are, in combination, significantly associated with subclinical and clinical cardiovascular outcomes. As knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events.
authors.affiliation: Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. a.isaacs@erasmusmc.nl
authors.forename: Aaron
authors.initials: A
authors.lastname: Isaacs
authors.forename: Sara M
authors.initials: SM
authors.lastname: Willems
authors.forename: Daniel
authors.initials: D
authors.lastname: Bos
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Witteman
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol
keywords: atherosclerosis; carotid artery plaque; carotid intima-media thickness; coronary disease; genetic screening; lipids; myocardial infarction