Association of genetic variants and incident coronary heart disease in multi-ethnic cohorts. The PAGE Study.

Publication Type:

Journal Article


Circulation. Cardiovascular genetics, Volume 4, Issue 69, p.661-672 (2011)


2011, Aged, Aged, 80 and over, Center-Authored Paper, Continental Population Groups, Coronary Disease, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, November 2011, Polymorphism, Single Nucleotide, Prospective Studies, Public Health Sciences Division


BACKGROUND: -Genome wide association studies identified several single nucleotide polymorphisms (SNPs) associated with prevalent coronary heart disease (CHD) but less is known of associations with incident CHD. The association of thirteen published CHD SNPs was examined in five ancestry groups of four large US prospective cohorts. METHODS AND RESULTS: -The analyses included incident coronary events over 9.1 to 15.7 average follow-up times in up to 26,617 white individuals (6,626 events), 8,018 African Americans (914 events), 1,903 Hispanics (113 events), 3,669 American Indians (595 events) and 885 Asian/Pacific Islanders (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 whites: 9p21 (rs10757278, p=4.7 x 10(-41)), 16q23.1 (rs2549513, p=0.0004), 6p24.1 (rs499818, p=0.0002), 2q36.3 (rs2943634, p=6.7 x 10(-6)), MTHFDIL (rs6922269, p=5.1 x 10(-10)), APOE (rs429358, p=2.7 x 10(-18)), ZNF627 (rs4804611, p=5.0 x 10(-8)), CXCL12 (rs501120, p=1.4 x 10(-6)) and LPL (rs268, p=2.7 x 10(-17)). The 9p21 region showed significant between-study heterogeneity, with larger effects in individuals aged 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 African Americans and associations varied in other US minorities. CONCLUSIONS: -Prospective analyses of white individuals replicated several reported cross-sectional CHD-SNP associations.