Title | Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: the PAGE study. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Franceschini, 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, Boerwinkle, E |
Journal | PLoS One |
Volume | 9 |
Issue | 12 |
Pagination | e113203 |
Date Published | 2014 |
ISSN | 1932-6203 |
Keywords | Adaptor Proteins, Vesicular Transport, Black or African American, 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. |
DOI | 10.1371/journal.pone.0113203 |
Alternate Journal | PLoS One |
PubMed ID | 25542012 |
PubMed Central ID | PMC4277270 |
Grant List | 32105-6 / / PHS HHS / United States HL59684 / HL / NHLBI NIH HHS / United States R01 CA082659 / CA / NCI NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States R01 HL071025 / HL / NHLBI NIH HHS / United States R01 NR008153 / NR / NINR NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States HL071025-01A1 / HL / NHLBI NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States U01 HG004790 / HG / NHGRI NIH HHS / United States HHSN268201100005G / HL / NHLBI NIH HHS / United States HHSN268201100008I / HL / NHLBI NIH HHS / United States U01 HG004802 / HG / NHGRI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States HL097698 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States N01AG62101 / AG / NIA NIH HHS / United States 42107-26 / / PHS HHS / United States 32115 / / PHS HHS / United States HHSN268201100011I / HL / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH 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 N01 AG062106 / AG / NIA NIH HHS / United States HL58625-01A1 / HL / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States U01HG004802 / HG / NHGRI NIH HHS / United States 32100-2 / / PHS HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States 24152 / / PHS HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States 42129-32 / / PHS HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States L30 HL097698 / HL / NHLBI NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States R21HL123677-01 / HL / NHLBI NIH HHS / United States HHSN268201100005I / HL / NHLBI NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States Z01 AG000949 / ImNIH / Intramural NIH HHS / United States U01 HG004803 / HG / NHGRI NIH HHS / United States 32118-32119 / / PHS HHS / United States M01 RR000052 / RR / NCRR NIH 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 U01 HL072518 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States Z01 AG007390 / ImNIH / Intramural NIH HHS / United States HHSN268200782096C / HL / NHLBI NIH HHS / United States Z01 AG000949-02 / AG / NIA NIH HHS / United States R01 HL059684 / HL / NHLBI NIH HHS / United States R21 HL123677 / HL / NHLBI NIH HHS / United States U01HG004801 / HG / NHGRI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States NR008153-01 / NR / NINR NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States N01AG62103 / AG / NIA NIH HHS / United States U01HG004790 / HG / NHGRI NIH HHS / United States U01 HG004798 / HG / NHGRI NIH HHS / United States HHSN268200782096C / HG / NHGRI NIH 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 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH 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 N01WH22110 / WH / WHI NIH HHS / United States R01 HL042630 / HL / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States U01 HG004801 / HG / NHGRI NIH HHS / United States |
Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: the PAGE study.
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