TY - JOUR
T1 - Genetic 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
AU - Hernesniemi, Jussi
AU - Seppälä, Ilkka
AU - Lyytikäinen, Leo-Pekka
AU - Mononen, Nina
AU - Oksala, Niku
AU - Hutri-Kähönen, Nina
AU - Juonala, Markus
AU - Taittonen, Leena
AU - Smith, Erin
AU - Schork, Nicholas
AU - Chen, Wei
AU - Srinivasan, Sathanur
AU - Berenson, Gerald
AU - Murray, Sarah
AU - Laitinen, Tomi
AU - Jula, Antti
AU - Kettunen, Johannes
AU - Ripatti, Samuli
AU - Laaksonen, Reijo
AU - Viikari, Jorma
AU - Kähönen, Mika
AU - Raitakari, Olli
AU - Lehtimäki, Terho
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0028931
DO - 10.1371/journal.pone.0028931
M3 - Article
AN - SCOPUS:84856292621
SN - 1932-6203
VL - 7
SP - e28931
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e28931
ER -