Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels

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. We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population...

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Veröffentlicht in:	Circulation (New York, N.Y.) Jg. 123; H. 7; S. 731
Hauptverfasser:	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, Zee, Robert Y L, Schnabel, Renate B, Nambi, Vijay, Kavousi, Maryam, Ripatti, Samuli, Nauck, Matthias, Smith, Nicholas L, Smith, Albert V, Sundvall, Jouko, Scheet, Paul, Liu, Yongmei, Ruokonen, Aimo, Rose, Lynda M, Larson, Martin G, Hoogeveen, Ron C, Freimer, Nelson B, Teumer, Alexander, Tracy, Russell P, Launer, Lenore J, Buring, Julie E, Yamamoto, Jennifer F, Folsom, Aaron R, Sijbrands, Eric J G, Pankow, James, Elliott, Paul, Keaney, John F, Sun, Wei, Sarin, Antti-Pekka, Fontes, João D, Badola, Sunita, Astor, Brad C, Hofman, Albert, Pouta, Anneli, Werdan, Karl, Greiser, Karin H, Kuss, Oliver, Meyer zu Schwabedissen, Henriette E, Thiery, Joachim, Jamshidi, Yalda, Nolte, Ilja M, Soranzo, Nicole, Spector, Timothy D, Völzke, Henry, Parker, Alexander N, Aspelund, Thor, Bates, David, Young, Lauren, Tsui, Kim, Siscovick, David S, Guo, Xiuqing, Rotter, Jerome I, Uda, Manuela, Schlessinger, David, Rudan, Igor, Hicks, Andrew A, Penninx, Brenda W, Thorand, Barbara, Gieger, Christian, Coresh, Joe, Willemsen, Gonneke, Harris, Tamara B, Uitterlinden, Andre G, Järvelin, Marjo-Riitta, Rice, Kenneth, Radke, Dörte, Salomaa, Veikko, Willems van Dijk, Ko, Boerwinkle, Eric, Vasan, Ramachandran S, Ferrucci, Luigi, Gibson, Quince D, Bandinelli, Stefania, Snieder, Harold, Boomsma, Dorret I, Xiao, Xiangjun, Campbell, Harry
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 22.02.2011
Schlagworte:	Biomarkers C-Reactive Protein - genetics Cardiovascular Diseases - epidemiology Cardiovascular Diseases - genetics Cardiovascular Diseases - immunology Genetic Predisposition to Disease - epidemiology Genome-Wide Association Study - statistics & numerical data Humans Risk Factors Vasculitis - epidemiology Vasculitis - genetics Vasculitis - immunology
ISSN:	1524-4539, 1524-4539
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Zusammenfassung:	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. 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 (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2) or the immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1) or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found a significant interaction of body mass index with LEPR (P<2.9×10(-6)). 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. 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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1524-4539 1524-4539
DOI:	10.1161/CIRCULATIONAHA.110.948570