title: Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study.
abstract: BACKGROUND
  Local ancestry in relation to clinical cardiovascular events (CVEs) among African Americans can provide insight into their genetic susceptibility to the disease.
  
  
  RESULTS
  We examined local European ancestry (LEA) association with CVEs among 3000 African Americans from the Atherosclerosis Risk in Communities Study (ARIC). We estimated LEA usingLocalAncestry Inference in adMixedPopulations usingLinkageDisequilibrium (LAMP-LD) and examined its association with myocardial infarction, stroke, coronary heart disease and its composite and cardiovascular disease composite using logistic regression. Genome-wide significance was achieved by 121 LEA regions in relation to myocardial infarction and 2 in relation to the cardiovascular disease composite. The LEA region downstream of 4q32.1 was significantly associated with 2 times higher odds of myocardial infarction (P=1.45×10-6). The LEA region upstream of 6q11.1 was associated with 0.37 times lower odds of fatal coronary heart disease (P=7.34×10-4), whereas the LEA region downstream of 21q21.1 was associated with 1.55 times higher odds of composite coronary heart disease (P=3.45×10-4). Association of LEA with stroke was observed in the region upstream of 6p22.3 with a 1.57 times higher odds of stroke (P=9.69×10-4). Likewise, the LEA region on 4q32.3 was associated with a 1.53 times higher odds of composite cardiovascular disease (P=3.04×10-4). We also found 20 of the LEA regions at previously significant cardiovascular disease single-nucleotide polymorphisms to be associated with CVE in our study.
  
  
  CONCLUSIONS
  Future studies are needed to replicate and/or determine the causal variants driving our associations and explore clinical applications for those consistently associated with CVEs.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, AL.
authors.forename: Aditi
authors.initials: A
authors.lastname: Shendre
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, AL.
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Irvin
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, AL.
authors.forename: Howard
authors.initials: H
authors.lastname: Wiener
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, AL.
authors.forename: Degui
authors.initials: D
authors.lastname: Zhi
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, AL.
authors.forename: Nita A
authors.initials: NA
authors.lastname: Limdi
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, AL.
authors.forename: Edgar T
authors.initials: ET
authors.lastname: Overton
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, AL sshrestha@uab.edu.
authors.forename: Sadeep
authors.initials: S
authors.lastname: Shrestha
mesh_terms: D001741:Black or African American / Q000235:genetics*; D050197:Atherosclerosis / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D040941:Heredity; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*
keywords: admixture mapping; association studies; cardiovascular events; genetic epidemiology; genetics; genome‐wide association scan; race and ethnicity