title: Association between parental history and genetic risk scores for coronary heart disease prediction: The population-based CoLaus study.
abstract: OBJECTIVE
  Parental history (PH) and genetic risk scores (GRSs) are separately associated with coronary heart disease (CHD), but evidence regarding their combined effects is lacking. We aimed to evaluate the joint associations and predictive ability of PH and GRSs for incident CHD.
  
  
  METHODS
  Data for 4283 Caucasians were obtained from the population-based CoLaus Study, over median follow-up time of 5.6 years. CHD was defined as incident myocardial infarction, angina, percutaneous coronary revascularization or bypass grafting. Single nucleotide polymorphisms for CHD identified by genome-wide association studies were used to construct unweighted and weighted versions of three GRSs, comprising of 38, 53 and 153 SNPs respectively.
  
  
  RESULTS
  PH was associated with higher values of all weighted GRSs. After adjustment for age, sex, smoking, diabetes, systolic blood pressure, low and high density lipoprotein cholesterol, PH was significantly associated with CHD [HR 2.61, 95% CI (1.47-4.66)] and further adjustment for GRSs did not change this estimate. Similarly, one standard deviation change of the weighted 153-SNPs GRS was significantly associated with CHD [HR 1.50, 95% CI (1.26-1.80)] and remained so, after further adjustment for PH. The weighted, 153-SNPs GRS, but not PH, modestly improved discrimination [(C-index improvement, 0.016), p = 0.048] and reclassification [(NRI improvement, 8.6%), p = 0.027] beyond cardiovascular risk factors. After including both the GRS and PH, model performance improved further [(C-index improvement, 0.022), p = 0.006].
  
  
  CONCLUSIONS
  After adjustment for cardiovascular risk factors, PH and a weighted, polygenic GRS were jointly associated with CHD and provided additive information for coronary events prediction.
authors.affiliation: Department of Internal Medicine, University Hospital of Lausanne (CHUV), Rue du Bugnon 21, 1011, Lausanne, Switzerland. Electronic address: panagiotis.antiochos@gmail.com.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Antiochos
authors.affiliation: Department of Internal Medicine, University Hospital of Lausanne (CHUV), Rue du Bugnon 21, 1011, Lausanne, Switzerland. Electronic address: Pedro-Manuel.Marques-Vidal@chuv.ch.
authors.forename: Pedro
authors.initials: P
authors.lastname: Marques-Vidal
authors.affiliation: Institute of Social and Preventive Medicine, University Hospital of Lausanne (CHUV), Rue du Bugnon 17, 1011, Lausanne, Switzerland. Electronic address: aaronmcdaid@gmail.com.
authors.forename: Aaron
authors.initials: A
authors.lastname: McDaid
authors.affiliation: Department of Internal Medicine, University Hospital of Lausanne (CHUV), Rue du Bugnon 21, 1011, Lausanne, Switzerland. Electronic address: Gerard.Waeber@chuv.ch.
authors.forename: Gerard
authors.initials: G
authors.lastname: Waeber
authors.affiliation: Department of Internal Medicine, University Hospital of Lausanne (CHUV), Rue du Bugnon 21, 1011, Lausanne, Switzerland. Electronic address: Peter.Vollenweider@chuv.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
mesh_terms: D003324:Coronary Artery Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010290:Parents; D011159:Population Surveillance; D011446:Prospective Studies; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology
keywords: Coronary heart disease; Genetic risk score; Parental history; Prospective study; Reclassification