Meta-Analysis of Genome-Wide Association Studies in 80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels

Medientyp: E-Artikel
Titel: Meta-Analysis of Genome-Wide Association Studies in 80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels
Beteiligte: Dehghan, Abbas; Dupuis, Josée; Barbalic, Maja; Bis, Joshua C.; Eiriksdottir, Gudny; Lu, Chen; Pellikka, Niina; Wallaschofski, Henri; Kettunen, Johannes; Henneman, Peter; Baumert, Jens; Strachan, David P.; Fuchsberger, Christian; Vitart, Veronique; Wilson, James F.; Paré, Guillaume; Naitza, Silvia; Rudock, Megan E.; Surakka, Ida; de Geus, Eco J.C.; Alizadeh, Behrooz Z.; Guralnik, Jack; Shuldiner, Alan; Tanaka, Toshiko; [...]
Erschienen: Ovid Technologies (Wolters Kluwer Health), 2011
Erschienen in: Circulation
Sprache: Englisch
DOI: 10.1161/circulationaha.110.948570
ISSN: 0009-7322; 1524-4539
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Beschreibung: <jats:sec> <jats:title>Background—</jats:title> <jats:p>C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome ( <jats:italic>APOC1</jats:italic> , <jats:italic>HNF1A</jats:italic> , <jats:italic>LEPR</jats:italic> , <jats:italic>GCKR</jats:italic> , <jats:italic>HNF4A</jats:italic> , and <jats:italic>PTPN2</jats:italic> ) or the immune system ( <jats:italic>CRP</jats:italic> , <jats:italic>IL6R</jats:italic> , <jats:italic>NLRP3</jats:italic> , <jats:italic>IL1F10</jats:italic> , and <jats:italic>IRF1</jats:italic> ) or that reside in regions previously not known to play a role in chronic inflammation ( <jats:italic>PPP1R3B</jats:italic> , <jats:italic>SALL1</jats:italic> , <jats:italic>PABPC4</jats:italic> , <jats:italic>ASCL1</jats:italic> , <jats:italic>RORA</jats:italic> , and <jats:italic>BCL7B</jats:italic> ). We found a significant interaction of body mass index with <jats:italic>LEPR</jats:italic> ( <jats:italic>P</jats:italic> <2.9×10 <jats:sup>−6</jats:sup> ). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained ≈5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.</jats:p> </jats:sec>
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