title: The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts.
abstract: 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.
authors.affiliation: Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland. juha.karvanen@ktl.fi
authors.forename: Juha
authors.initials: J
authors.lastname: Karvanen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Silander
authors.forename: Frank
authors.initials: F
authors.lastname: Kee
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Kari
authors.initials: K
authors.lastname: Kuulasmaa
authors.forename: Per-Gunnar
authors.initials: PG
authors.lastname: Wiklund
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Olli
authors.initials: O
authors.lastname: Saarela
authors.forename: Claire
authors.initials: C
authors.lastname: Perret
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Francois
authors.initials: F
authors.lastname: Cambien
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Alun
authors.initials: A
authors.lastname: Evans
mesh_terms: D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015331:Cohort Studies; D003327:Coronary Disease / Q000235:genetics*; D005387:Finland / Q000453:epidemiology; D005602:France / Q000453:epidemiology; D006801:Humans; D009026:Mortality; D009660:Northern Ireland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology