Meta-Analysis of Genome-Wide Association Studies in >80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels
| Autor: | Kenneth Rice, Veronique Vitart, Toshiko Tanaka, Stefania Bandinelli, Julie E. Buring, Oliver Kuss, Luigi Ferrucci, Behrooz Z. Alizadeh, Eric J.G. Sijbrands, Anneli Pouta, Dörte Radke, Brenda W.J.H. Penninx, Gonneke Willemsen, Maryam Kavousi, Russell P. Tracy, Henriette E. Meyer zu Schwabedissen, Aaron R. Folsom, Dorret I. Boomsma, Harry Campbell, Xiuqing Guo, Karl Werdan, Josée Dupuis, Vilmundur Gudnason, Igor Rudan, Jacqueline C.M. Witteman, Martin G. Larson, João D. Fontes, Paul Scheet, John F. Keaney, Joachim Thiery, Harold Snieder, Albert Hofman, Manuela Uda, Niina Pellikka, Robert Y.L. Zee, Quince Gibson, Christie M. Ballantyne, David P. Strachan, Thor Aspelund, Eric Boerwinkle, Cornelia M. van Duijn, Samuli Ripatti, Ko Willems van Dijk, Brad C. Astor, Ilja M. Nolte, Caroline Hayward, Alex Parker, Antti-Pekka Sarin, Ida Surakka, Paul M. Ridker, David S. Siscovick, Veikko Salomaa, Sunita Badola, Andrew A. Hicks, Barbara Thorand, Megan E. Rudock, Joshua C. Bis, Daniel I. Chasman, Maja Barbalić, Karin Halina Greiser, Yongmei Liu, Alexander Teumer, Ramachandran S. Vasan, Jouko Sundvall, Lauren Young, Jack M. Guralnik, Ron C. Hoogeveen, Nicole Soranzo, Nicholas L. Smith, Nelson B. Freimer, Gudny Eiriksdottir, Paul Elliott, Henri Wallaschofski, Peter Henneman, James F. Wilson, Markus Perola, Bruce M. Psaty, Wolfgang Koenig, Lenore J. Launer, Leena Peltonen, Joe Coresh, Matthias Nauck, Kim Tsui, Yalda Jamshidi, Jens Baumert, Henry Völzke, Xiangjun Xiao, Abbas Dehghan, Christian Fuchsberger, Silvia Naitza, Christian Gieger, Renate B. Schnabel, Johannes Kettunen, Lynda M. Rose, Albert V. Smith, Peter P. Pramstaller, Chen Lu, Emelia J. Benjamin, Alan R. Shuldiner, Eco J. C. de Geus, Aimo Ruokonen, Tamara B. Harris, David W. Bates, Wei Sun, James S. Pankow, Jerome I. Rotter, Vijay Nambi, Marjo-Riitta Järvelin, Guillaume Paré, David Schlessinger, Jennifer F. Yamamoto, Tim D. Spector, Georg Homuth, André G. Uitterlinden |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, Psychiatry, EMGO - Mental health, NCA - Anxiety & Depression, Epidemiology, Internal Medicine, Public Health |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Netherlands Twin Register (NTR)
Genome-wide association study Disease 030204 cardiovascular system & hematology 0302 clinical medicine DESIGN Risk Factors FRAMINGHAM NETHERLANDS TWIN REGISTER genetics CRP GENE 2. Zero hunger Genetics 0303 health sciences education.field_of_study biology COMMON VARIANTS 3. Good health HNF1A C-Reactive Protein myocardial infarction Cardiovascular Diseases Meta-analysis Cardiology and Cardiovascular Medicine Vasculitis Population Article 03 medical and health sciences INFLAMMATION SDG 3 - Good Health and Well-being Physiology (medical) medicine Humans Genetic Predisposition to Disease CORONARY-HEART-DISEASE ALPHA-GENE education 030304 developmental biology Genetic association EPIDEMIOLOGIC APPLICATIONS genome-wide association study C-reactive protein medicine.disease meta-analysis inflammation biology.protein GENETICALLY ISOLATED POPULATION Metabolic syndrome Biomarkers |
| Zdroj: | Dehghan, A, Dupuis, J, Barbalic, M, Bis, J C, Eiriksdottir, G, Lu, C, Pellikka, N, Wallaschofski, H, Kettunen, J, Henneman, P, Baumert, J, Strachan, D P, Fuchsberger, C, Vitart, V, Wilson, J F, Paré, G, Naitza, S, Rudock, M E, Surakka, I, de Geus, E J C, Alizadeh, BZ, Guralnik, J, Shuldiner, A, Tanaka, T, Zee, R Y L, Schnabel, R B, Nambi, V, Kavousi, M, Ripatti, S, Nauck, M, Smith, N L, Smith, A V, Sundvall, J, Scheet, P, Liu, Y, Ruokonen, A, Rose, L M, Larson, M G, Hoogeveen, R C, Freimer, N B, Teumer, A, Tracy, R P, Launer, L J, Buring, J E, Yamamoto, J F, Folsom, A R, Sijbrands, E J G, Pankow, J, Elliott, P, Keaney, J F, Sun, W, Sarin, A-P, Fontes, J D, Badola, S, Astor, B C, Hofman, A, Pouta, A, Werdan, K, Greiser, K H, Meyer zu Schwabedissen, H E, Thiery, J, Jamshidi, Y, Nolte, I M, Soranzo, N, Spector, T D, Völzke, H, Aspelund, T, Young, L, Siscovick, D S, Rotter, J I, Schlessinger, D, Rudan, I, Hicks, A A, Penninx, B W J H, Gieger, C, Willemsen, G, Harris, T B, Uitterlinden, A G, Järvelin, M J, Rice, K, Salomaa, V, Boerwinkle, E, Ferrucci, L, Snieder, H, Boomsma, D I, Hayward, C, Pramstaller, P P, van Duijn, C M, Peltonen, L, Psaty, B M, Gudnason, V, Ridker, P M, Homuth, G, Koenig, W, Ballantyne, C M, Witteman, J C M, Benjamin, E J, Perola, M & Chasman, D I 2011, ' Meta-Analysis of Genome-Wide Association Studies in >80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels ', Circulation, vol. 123, no. 7, pp. 731-738 . https://doi.org/10.1161/CIRCULATIONAHA.110.948570 Circulation, 123(7), 731-738. LIPPINCOTT WILLIAMS & WILKINS Circulation; Vol 123 Circulation Circulation, 123(7), 731-738. American Heart Association Circulation, 123(7), 731-738. Lippincott Williams and Wilkins Dehghan, A, Dupuis, J, Barbalic, M, Bis, J C, Eiriksdottir, G, Lu, C, Pellikka, N, Wallaschofski, H, Kettunen, J, Henneman, P, Baumert, J, Strachan, D P, Fuchsberger, C, Vitart, V, Wilson, J F, Pare, G, Naitza, S, Rudock, M E, Surakka, I, de Geus, E J C, Alizadeh, B Z, Guralnik, J, Shuldiner, A, Tanaka, T, Zee, R Y L, Schnabel, R B, Nambi, V, Kavousi, M, Ripatti, S, Nauck, M, Smith, N L, Smith, A V, Sundvall, J, Scheet, P, Liu, Y, Ruokonen, A, Rose, L M, Larson, M G, Hoogeveen, R C, Freimer, N B, Teumer, A, Tracy, R P, Launer, L J, Buring, J E, Yamamoto, J F, Folsom, A R, Sijbrands, E J G, Pankow, J, Elliott, P, Keaney, J F, Sun, W, Sarin, A-P, Fontes, J D, Badola, S, Astor, B C, Hofman, A, Pouta, A, Werdan, K, Greiser, K H, Kuss, O, Schwabedissen, H E M Z, Thiery, J, Jamshidi, Y, Nolte, I M, Soranzo, N, Spector, T D, Voelzke, H, Parker, A N, Aspelund, T, Bates, D, Young, L, Tsui, K, Siscovick, D S, Guo, X, Rotter, J I, Uda, M, Schlessinger, D, Rudan, I, Hicks, A A, Penninx, B W, Thorand, B, Gieger, C, Coresh, J, Willemsen, G, Harris, T B, Uitterlinden, A G, Jaervelin, M-R, Rice, K, Radke, D, Salomaa, V, van Dijk, K W, Boerwinkle, E, Vasan, R S, Ferrucci, L, Gibson, Q D, Bandinelli, S, Snieder, H, Boomsma, D I, Xiao, X, Campbell, H, Hayward, C, Pramstaller, P P, van Duijn, C M, Peltonen, L, Psaty, B M, Gudnason, V, Ridker, P M, Homuth, G, Koenig, W, Ballantyne, C M, Witteman, J C M, Benjamin, E J, Perola, M & Chasman, D I 2011, ' Meta-Analysis of Genome-Wide Association Studies in > 80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels ', Circulation, vol. 123, no. 7, pp. 731-U151 . https://doi.org/10.1161/CIRCULATIONAHA.110.948570 Circulation, 123(7), 731-U151 Circulation, 123(7), 731-U151. Lippincott Williams & Wilkins |
| ISSN: | 0009-7322 |
| Popis: | Background— 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. Methods and Results— 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 −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. Conclusions— 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. |
| Databáze: | OpenAIRE |
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