title: Lack of associations of ten candidate coronary heart disease risk genetic variants and subclinical atherosclerosis in four US populations: the Population Architecture using Genomics and Epidemiology (PAGE) study.
abstract: BACKGROUND
  A number of genetic variants have been discovered by recent genome-wide association studies for their associations with clinical coronary heart disease (CHD). However, it is unclear whether these variants are also associated with the development of CHD as measured by subclinical atherosclerosis phenotypes, ankle brachial index (ABI), carotid artery intima-media thickness (cIMT) and carotid plaque.
  
  
  METHODS
  Ten CHD risk single nucleotide polymorphisms (SNPs) were genotyped in individuals of European American (EA), African American (AA), American Indian (AI), and Mexican American (MA) ancestry in the Population Architecture using Genomics and Epidemiology (PAGE) study. In each individual study, we performed linear or logistic regression to examine population-specific associations between SNPs and ABI, common and internal cIMT, and plaque. The results from individual studies were meta-analyzed using a fixed effect inverse variance weighted model.
  
  
  RESULTS
  None of the ten SNPs was significantly associated with ABI and common or internal cIMT, after Bonferroni correction. In the sample of 13,337 EA, 3809 AA, and 5353 AI individuals with carotid plaque measurement, the GCKR SNP rs780094 was significantly associated with the presence of plaque in AI only (OR = 1.32, 95% confidence interval: 1.17, 1.49, P = 1.08 × 10(-5)), but not in the other populations (P = 0.90 in EA and P = 0.99 in AA). A 9p21 region SNP, rs1333049, was nominally associated with plaque in EA (OR = 1.07, P = 0.02) and in AI (OR = 1.10, P = 0.05).
  
  
  CONCLUSIONS
  We identified a significant association between rs780094 and plaque in AI populations, which needs to be replicated in future studies. There was little evidence that the index CHD risk variants identified through genome-wide association studies in EA influence the development of CHD through subclinical atherosclerosis as assessed by cIMT and ABI across ancestries.
authors.affiliation: Department of Internal Medicine, Jacobi Medical Center, Bronx, NY, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Petra
authors.initials: P
authors.lastname: Buzkova
authors.forename: Christina L
authors.initials: CL
authors.lastname: Wassel
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Roman
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Jonathan
authors.initials: J
authors.lastname: Boston
authors.forename: Kristin D
authors.initials: KD
authors.lastname: Brown-Gentry
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Ewa
authors.initials: E
authors.lastname: Deelman
authors.forename: Robert
authors.initials: R
authors.lastname: Goodloe
authors.forename: Sarah
authors.initials: S
authors.lastname: Wilson
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Neal W
authors.initials: NW
authors.lastname: Jorgensen
authors.forename: Tara C
authors.initials: TC
authors.lastname: Matise
authors.forename: Bob E
authors.initials: BE
authors.lastname: McClellan
authors.forename: Alejandro Q
authors.initials: AQ
authors.lastname: Nato
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D055109:Ankle Brachial Index; D058070:Asymptomatic Diseases; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D003327:Coronary Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics