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Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: the PAGE study.

TitleProspective associations of coronary heart disease loci in African Americans using the MetaboChip: the PAGE study.
Publication TypeJournal Article
Year of Publication2014
AuthorsFranceschini N, Hu Y, Reiner AP, Buyske S, Nalls M, Yanek LR, Li Y, Hindorff LA, Cole SA, Howard BV, Stafford JM, Carty CL, Sethupathy P, Martin LW, Lin D-Y, Johnson KC, Becker LC, North KE, Dehghan A, Bis JC, Liu Y, Greenland P, Manson JAE, Maeda N, Garcia M, Harris TB, Becker DM, O'Donnell C, Heiss G, Kooperberg C
Secondary AuthorsBoerwinkle E
JournalPLoS One
Volume9
Issue12
Paginatione113203
Date Published2014
ISSN1932-6203
KeywordsAdaptor Proteins, Vesicular Transport, African Americans, Coronary Disease, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Prospective Studies, Proto-Oncogene Proteins c-myc
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.

METHODS AND 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.

DOI10.1371/journal.pone.0113203
Alternate JournalPLoS One
PubMed ID25542012
PubMed Central IDPMC4277270
Grant ListR01 CA082659 / CA / NCI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
32105-6 / / PHS HHS / United States
N01WH22110 / WH / WHI NIH HHS / United States
HL59684 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HL071025-01A1 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HL097698 / HL / NHLBI NIH HHS / United States
N01AG62101 / AG / NIA NIH HHS / United States
42107-26 / / PHS HHS / United States
32115 / / PHS HHS / United States
U01 HG007376 / HG / NHGRI NIH HHS / United States
U01HG004803 / HG / NHGRI NIH HHS / United States
1R01AG032098-01A1 / AG / NIA NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
HL58625-01A1 / HL / NHLBI NIH HHS / United States
U01HG004802 / HG / NHGRI NIH HHS / United States
32100-2 / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
24152 / / PHS HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
/ / Intramural NIH HHS / United States
42129-32 / / PHS HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
R21HL123677-01 / HL / NHLBI NIH HHS / United States
32118-32119 / / PHS HHS / United States
U01HG004798 / HG / NHGRI NIH HHS / United States
NR0224103 / NR / NINR NIH HHS / United States
U01 HL72518 / HL / NHLBI NIH HHS / United States
32108-9 / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
Z01 AG000949-02 / AG / NIA NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
U01HG004801 / HG / NHGRI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
NR008153-01 / NR / NINR NIH HHS / United States
N01AG62103 / AG / NIA NIH HHS / United States
U01HG004790 / HG / NHGRI NIH HHS / United States
HHSN268200782096C / / PHS HHS / United States
N01AG62106 / AG / NIA NIH HHS / United States
32122 / / PHS HHS / United States
Z01 AG007390-07 / AG / NIA NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
44221 / / PHS HHS / United States
H5254-12688-11 / / PHS HHS / United States
R01 HL109301 / HL / NHLBI NIH HHS / United States
M01 RR00052 / RR / NCRR NIH HHS / United States
32111-13 / / PHS HHS / United States
HSN268201100009C / / PHS HHS / United States
R01 HL042630 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States