Open AccessGenetic Profiling Using Genome-Wide Significant Coronary Artery Disease Risk Variants Does Not Improve the Prediction of Subclinical Atherosclerosis: The Cardiovascular Risk in Young Finns Study, the Bogalusa Heart Study and the Health 2000 Survey – A Meta-Analysis of Three Independent Studies
Author(s) -
Jussi Hernesniemi,
Ilkka Seppälä,
LeoPekka Lyytikäinen,
Nina Mon,
Niku Oksala,
Nina HutriKähönen,
Markus Juonala,
Leena Taittonen,
Erin N. Smith,
Nicholas J. Schork,
Wei Chen,
Sathanur R. Srinivasan,
Gerald S. Berenson,
Sarah Murray,
Tomi Laitinen,
Antti Jula,
Johannes Kettunen,
Samuli Ripatti,
Reijo Laaksonen,
Jorma Viikari,
Mika Kähönen,
Olli T. Raitakari,
Terho Lehtimäki
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0028931
Subject(s) - coronary artery disease , genome wide association study , medicine , single nucleotide polymorphism , population , subclinical infection , cardiology , genetic association , intima media thickness , odds ratio , genetics , genotype , biology , carotid arteries , environmental health , gene
Background Genome-wide association studies (GWASs) have identified a large number of variants (SNPs) associating with an increased risk of coronary artery disease (CAD). Recently, the CARDIoGRAM consortium published a GWAS based on the largest study population so far. They successfully replicated twelve already known associations and discovered thirteen new SNPs associating with CAD. We examined whether the genetic profiling of these variants improves prediction of subclinical atherosclerosis – i.e., carotid intima-media thickness (CIMT) and carotid artery elasticity (CAE) – beyond classical risk factors. Subjects and Methods We genotyped 24 variants found in a population of European ancestry and measured CIMT and CAE in 2001 and 2007 from 2,081, and 2,015 subjects (aged 30–45 years in 2007) respectively, participating in the Cardiovascular Risk in Young Finns Study (YFS). The Bogalusa Heart Study (BHS; n = 1179) was used as a replication cohort (mean age of 37.5). For additional replication, a sub-sample of 5 SNPs was genotyped for 1,291 individuals aged 46–76 years participating in the Health 2000 population survey. We tested the impact of genetic risk score (GRS 24SNP/CAD ) calculated as a weighted (by allelic odds ratios for CAD) sum of CAD risk alleles from the studied 24 variants on CIMT, CAE, the incidence of carotid atherosclerosis and the progression of CIMT and CAE during a 6-year follow-up. Results CIMT or CAE did not significantly associate with GRS 24SNP/CAD before or after adjusting for classical CAD risk factors (p>0.05 for all) in YFS or in the BHS. CIMT and CAE associated with only one SNP each in the YFS. The findings were not replicated in the replication cohorts. In the meta-analysis CIMT or CAE did not associate with any of the SNPs. Conclusion Genetic profiling, by using known CAD risk variants, should not improve risk stratification for subclinical atherosclerosis beyond conventional risk factors among healthy young adults.