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The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts
Author(s) -
Karvanen Juha,
Silander Kaisa,
Kee Frank,
Tiret Laurence,
Salomaa Veikko,
Kuulasmaa Kari,
Wiklund PerGunnar,
Virtamo Jarmo,
Saarela Olli,
Perret Claire,
Perola Markus,
Peltonen Leena,
Cambien Francois,
Erdmann Jeanette,
Samani Nilesh J.,
Schunkert Heribert,
Evans Alun
Publication year - 2009
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20374
Subject(s) - single nucleotide polymorphism , medicine , prospective cohort study , genome wide association study , snp , stroke (engine) , genetics , biology , genotype , gene , mechanical engineering , engineering
Recently, genome wide association studies (GWAS) have identified a number of single nucleotide polymorphisms (SNPs) as being associated with coronary heart disease (CHD). We estimated the effect of these SNPs on incident CHD, stroke and total mortality in the prospective cohorts of the MORGAM Project. We studied cohorts from Finland, Sweden, France and Northern Ireland (total N =33,282, including 1,436 incident CHD events and 571 incident stroke events). The lead SNPs at seven loci identified thus far and additional SNPs (in total 42) were genotyped using a case‐cohort design. We estimated the effect of the SNPs on disease history at baseline, disease events during follow‐up and classic risk factors. Multiple testing was taken into account using false discovery rate (FDR) analysis. SNP rs1333049 on chromosome 9p21.3 was associated with both CHD and stroke (HR=1.20, 95% CI 1.08–1.34 for incident CHD events and 1.15, 0.99–1.34 for incident stroke). SNP rs11670734 (19q12) was associated with total mortality and stroke. SNP rs2146807 (10q11.21) showed some association with the fatality of acute coronary event. SNP rs2943634 (2q36.3) was associated with high density lipoprotein (HDL) cholesterol and SNPs rs599839, rs4970834 (1p13.3) and rs17228212 (15q22.23) were associated with non‐HDL cholesterol. SNPs rs2943634 (2q36.3) and rs12525353 (6q25.1) were associated with blood pressure. These findings underline the need for replication studies in prospective settings and confirm the candidacy of several SNPs that may play a role in the etiology of cardiovascular disease. Genet. Epidemiol . 2009. © 2008 Wiley‐Liss, Inc.