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

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dc.contributor.author Hernesniemi, Jussi -
dc.contributor.author Seppälä, Ilkka -
dc.contributor.author Lyytikäinen, Leo-Pekka -
dc.contributor.author Mononen, Nina -
dc.contributor.author Oksala, Niku -
dc.contributor.author Hutri-Kähönen, Nina -
dc.contributor.author Laaksonen, Reijo -
dc.contributor.author Kähönen, Mika -
dc.contributor.author Lehtimäki, Terho -
dc.date.accessioned 2012-06-17T20:15:25Z
dc.date.available 2012-06-17 16:57:32 -
dc.date.available 2012-06-17T20:15:25Z
dc.date.issued 2012 -
dc.identifier.issn 1932-6203 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/66086
dc.description Public Library of Science open access -
dc.description.abstract 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 (GRS24SNP/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 GRS24SNP/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. -
dc.language.iso en -
dc.title 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 -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-915 -
dc.identifier.doi 10.1371/journal.pone.0028931 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Biolääketieteet | en=Biomedicine| -
dc.administrativeunit fi=Biolääketieteellisen teknologian yksikkö | en=Institute of Biomedical Technology| -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.journal.title Plos ONE -
dc.journal.volume 7 -
dc.journal.number 1 -
dc.journal.volumepagerange 1-10 -
dc.oldstats 50 -

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