title: Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: the PAGE study.
abstract: BACKGROUND
  Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans.
  
  
  RESULTS
  Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P = 8.1 × 10(-8)), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium.
  
  
  CONCLUSIONS
  Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.
authors.affiliation: Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, United States of America; Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Reiner
authors.affiliation: Department of Statistics & Biostatistics, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Buyske
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, Maryland, United States of America.
authors.forename: Mike
authors.initials: M
authors.lastname: Nalls
authors.affiliation: Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Yanek
authors.affiliation: Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, United States of America.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.affiliation: MedStar Health Research Institute, Hyattsville, Maryland, United States of America.
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Stafford
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Cara L
authors.initials: CL
authors.lastname: Carty
authors.affiliation: Department of Genetics Lineberger Comprehensive Cancer Center School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Praveen
authors.initials: P
authors.lastname: Sethupathy
authors.affiliation: Cardiovascular Institute, the George Washington University, Washington, D. C., United States of America.
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.affiliation: Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Dan-Yu
authors.initials: DY
authors.lastname: Lin
authors.affiliation: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.affiliation: Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
authors.affiliation: Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America; UNC Center for Genome Sciences, Chapel Hill, North Carolina, United States of America.
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.affiliation: Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.affiliation: Center for Human Genomics, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston Salem, North Carolina, Tennessee, United States of America.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Departments of Preventive Medicine and Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Philip
authors.initials: P
authors.lastname: Greenland
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, Maryland, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, Maryland, United States of America.
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Becker
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Donnell
authors.affiliation: Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.affiliation: Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D001741:Black or African American / Q000235:genetics*; D003327:Coronary Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016271:Proto-Oncogene Proteins c-myc; D000099183:Sortilin; C489427:MYC protein, human