title: Impact of adding a single allele in the 9p21 locus to traditional risk factors on reclassification of coronary heart disease risk and implications for lipid-modifying therapy in the Atherosclerosis Risk in Communities study.
abstract: BACKGROUND
  A single-nucleotide polymorphism on chromosome 9p21, rs10757274 (9p21 allele), has been shown to predict coronary heart disease (CHD) in whites. We evaluated whether adding the 9p21 allele to traditional risk factors (RFs) improved CHD risk prediction in whites from the Atherosclerosis Risk in Communities study and whether changes in risk prediction would modify lipid therapy recommendations.
  
  
  RESULTS
  Whites (n=9998) in the Atherosclerosis Risk in Communities study for whom the 9p21 genotype and traditional RF information was available were included. Using Cox proportional hazards models, the Atherosclerosis Risk in Communities Cardiovascular Risk Score, which is based on traditional RFs, was determined. A total of 1349 individuals (13.5%) developed incident CHD events during a period of 14.6 years. Adding the 9p21 allele to traditional RFs was associated with a hazard ratio of incident CHD of 1.2 per allele (P<0.000003) and a significant increase in the area under the curve of the receiver operating characteristic from 0.782 to 0.786 (95% CI, 0.001, 0.007). The 9p21 allele's greatest influence to the Atherosclerosis Risk in Communities Cardiovascular Risk Score was observed in the intermediate-low (>5% to <or=10% 10-year CHD risk) and intermediate-high (>10% to <or=20% 10-year CHD risk) categories, with 12.1% and 12.6% reclassified, respectively. This may impact therapy because 90% of these reclassified individuals had low-density lipoprotein cholesterol >100 mg/dL.
  
  
  CONCLUSIONS
  Adding the 9p21 allele to traditional RFs in whites in the Atherosclerosis Risk in Communities study modestly improved CHD risk prediction in the intermediate categories.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Brautbar
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Kim
authors.initials: K
authors.lastname: Lawson
authors.forename: Vijay
authors.initials: V
authors.lastname: Nambi
authors.forename: Lloyd
authors.initials: L
authors.lastname: Chambless
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
mesh_terms: D000483:Alleles; D050197:Atherosclerosis / Q000235:genetics / Q000628:therapy; D008078:Cholesterol, LDL / Q000032:analysis; D002899:Chromosomes, Human, Pair 9; D055812:Community-Based Participatory Research; D003327:Coronary Disease / Q000145:classification / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D008078:Cholesterol, LDL