Journal
CIRCULATION-CARDIOVASCULAR GENETICS
Volume 4, Issue 6, Pages 662-U387Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.111.960096
Keywords
9p21 locus; incident coronary heart disease; genetic polymorphisms
Funding
- National Human Genome Research Institute (NHGRI)
- CALiCo [U01HG004803]
- EAGLE [U01HG004798]
- MEC [U01HG004802]
- WHI [U01HG004790]
- Coordinating Center [U01HG004801]
- Epidemiology of Putative Genuine Genetic Variants
- Women's Health Initiative [U01HG004790]
- National Heart, Lung, and Blood Institute
- National Institutes of Health
- US Department of Health and Human Services [N01WH22110, 24152, 32100, 32102, 32105, 32106, 32108, 32109, 32111, 32113, 32115, 32118, 32119, 32122, 42107, 42126, 42129, 42132, 44221]
- CALiCo program was provided through the NHGRI PAGE program [U01HG004803]
- National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01HL080295, R01 HL087652]
- National Institutes of Health and National Heart, Lung and Blood Institute [N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205]
- National Center for Research Resources [M01RR00425]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- NHLBI [U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521]
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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=4.7X10(-41)), 16q23.1 (rs2549513; P=0.0004), 6p24.1 (rs499818; P=0.0002), 2q36.3 (rs2943634; P=6.7X10(-6)), MTHFD1L (rs6922269, P=5.1X10(-10)), APOE (rs429358; P=2.7X10(-18)), ZNF627 (rs4804611; P=5.0X10(-8)), CXCL12 (rs501120; P=1.4X10(-6)) and LPL (rs268; P=2.7X10(-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. (Circ Cardiovasc Genet. 2011;4:661-672.)
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