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

Nora Franceschini, Yijuan Hu, Alex P. Reiner, Steven Buyske, Mike Nalls, Lisa R. Yanek, Yun Li, Lucia A. Hindorff, Shelley A. Cole, Barbara V. Howard, Jeanette M. Stafford, Cara L. Carty, Praveen Sethupathy, Lisa W. Martin, Dan Yu Lin, Karen C. Johnson, Lewis C. Becker, Kari E. North, Abbas Dehghan, Joshua C. BisYongmei Liu, Philip Greenland, Jo Ann E. Manson, Nobuyo Maeda, Melissa Garcia, Tamara B. Harris, Diane M. Becker, Christopher O'Donnell, Gerardo Heiss, Charles Kooperberg, Eric Boerwinkle

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere113203
JournalPloS one
Volume9
Issue number12
DOIs
StatePublished - Dec 26 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Franceschini, N., Hu, Y., Reiner, A. P., Buyske, S., Nalls, M., Yanek, L. R., Li, Y., Hindorff, L. A., Cole, S. A., Howard, B. V., Stafford, J. M., Carty, C. L., Sethupathy, P., Martin, L. W., Lin, D. Y., Johnson, K. C., Becker, L. C., North, K. E., Dehghan, A., ... Boerwinkle, E. (2014). Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: The PAGE study. PloS one, 9(12), [e113203]. https://doi.org/10.1371/journal.pone.0113203