Key result
Nine genetic loci including 9p21 are linked to incident CHD in white but not black participants.
Why the study?
Genome-wide association studies identified SNPs associated with prevalent CHD, but less is known about their association with incident CHD across diverse ancestries.
Are previously published coronary heart disease SNPs associated with incident coronary heart disease across different ancestry groups in US prospective cohorts?
Cohort (n=41,092)
Yes
Are previously published coronary heart disease SNPs associated with incident coronary heart disease across different ancestry groups in US prospective cohorts?
Prospective analyses replicated several reported cross-sectional CHD-SNP associations in white participants, but these associations were not observed in black participants and varied in other US minorities.
Answers are grounded in this paper and cite their sources.
Replicates several CHD SNPs for incident events in whites but not blacks; leaves open ancestry-specific genetic risk prediction.
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.
No takes yet. Share an insight, caveat, or question.
Franceschini et al. (2011) conducted a cohort in Incident coronary heart disease (n=41,092). 13 published CHD single nucleotide polymorphisms (SNPs) was evaluated on Incident coronary events (p=4.7 × 10(-41)). Nine genetic loci, including 9p21, were significantly associated with incident coronary heart disease events in white participants (P=4.7 × 10(-41) for 9p21), but not in black participants.
Synapse has enriched 10 related papers. Consider them for comparative context: