Association of genetic variants and incident coronary heart disease in multiethnic cohorts: The PAGE study

Nora Franceschini, Cara Carty, Petra Bužková, Alex P. Reiner, Tiana Garrett, Yi Lin, Jens S. Vöckler, Lucia A. Hindorff, Shelley A. Cole, Eric Boerwinkle, Dan Yu Lin, Ebony Bookman, Lyle G. Best, Jonathan N. Bella, Charles Eaton, Philip Greenland, Nancy Jenny, Kari E. North, Darin Taverna, Alicia M. YoungEwa Deelman, Charles Kooperberg, Bruce Psaty, Gerardo Heiss*

*Corresponding author for this work

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Background-Genome-wide association studies identified several single nucleotide polymorphisms (SNP) associated with prevalent coronary heart disease (CHD), but less is known of associations with incident CHD. The association of 13 published CHD SNPs was examined in 5 ancestry groups of 4 large US prospective cohorts. Methods and Results-The analyses included incident coronary events over an average 9.1 to 15.7 follow-up person-years in up to 26 617 white individuals (6626 events), 8018 black individuals (914 events), 1903 Hispanic individuals (113 events), 3669 American Indian individuals (595 events), and 885 Asian/Pacific Islander individuals (66 events). We used Cox proportional hazards models (with additive mode of inheritance) adjusted for age, sex, and ancestry (as needed). Nine loci were statistically associated with incident CHD events in white participants: 9p21 (rs10757278; P=4.7×10 -41), 16q23.1 (rs2549513; P=0.0004), 6p24.1 (rs499818; P=0.0002), 2q36.3 (rs2943634; P=6.7×10 -6), MTHFD1L (rs6922269, P=5.1×10 -10), APOE (rs429358; P=2.7×10 -18), ZNF627 (rs4804611; P=5.0×10 -8), CXCL12 (rs501120; P=1.4×10 -6) and LPL (rs268; P=2.7×10 -17). The 9p21 region showed significant between- study heterogeneity, with larger effects in individuals age 55 years or younger and in women. Inclusion of coronary revascularization procedures among the incident CHD events introduced heterogeneity. The SNPs were not associated with CHD in black participants, and associations varied in other US minorities. Conclusions-Prospective analyses of white participants replicated several reported cross-sectional CHD-SNP associations.

Original languageEnglish (US)
Pages (from-to)661-672
Number of pages12
JournalCirculation: Cardiovascular Genetics
Volume4
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • 9p21 locus
  • Genetic polymorphisms
  • Incident coronary heart disease

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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    Franceschini, N., Carty, C., Bužková, P., Reiner, A. P., Garrett, T., Lin, Y., Vöckler, J. S., Hindorff, L. A., Cole, S. A., Boerwinkle, E., Lin, D. Y., Bookman, E., Best, L. G., Bella, J. N., Eaton, C., Greenland, P., Jenny, N., North, K. E., Taverna, D., ... Heiss, G. (2011). Association of genetic variants and incident coronary heart disease in multiethnic cohorts: The PAGE study. Circulation: Cardiovascular Genetics, 4(6), 661-672. https://doi.org/10.1161/CIRCGENETICS.111.960096