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

Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
TitleMeta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.
Publication TypeJournal Article
Year of Publication2011
AuthorsDehghan, A, Dupuis, J, Barbalic, M, Bis, JC, Eiriksdottir, G, Lu, C, Pellikka, N, Wallaschofski, H, Kettunen, J, Henneman, P, Baumert, J, Strachan, DP, Fuchsberger, C, Vitart, V, Wilson, JF, Paré, G, Naitza, S, Rudock, ME, Surakka, I, de Geus, EJC, Alizadeh, BZ, Guralnik, J, Shuldiner, A, Tanaka, T, Zee, RYL, Schnabel, RB, Nambi, V, Kavousi, M, Ripatti, S, Nauck, M, Smith, NL, Smith, AV, Sundvall, J, Scheet, P, Liu, Y, Ruokonen, A, Rose, LM, Larson, MG, Hoogeveen, RC, Freimer, NB, Teumer, A, Tracy, RP, Launer, LJ, Buring, JE, Yamamoto, JF, Folsom, AR, Sijbrands, EJG, Pankow, J, Elliott, P, Keaney, JF, Sun, W, Sarin, A-P, Fontes, JD, Badola, S, Astor, BC, Hofman, A, Pouta, A, Werdan, K, Greiser, KH, Kuss, O, Meyer zu Schwabedissen, HE, Thiery, J, Jamshidi, Y, Nolte, IM, Soranzo, N, Spector, TD, Völzke, H, Parker, AN, Aspelund, T, Bates, D, Young, L, Tsui, K, Siscovick, DS, Guo, X, Rotter, JI, Uda, M, Schlessinger, D, Rudan, I, Hicks, AA, Penninx, BW, Thorand, B, Gieger, C, Coresh, J, Willemsen, G, Harris, TB, Uitterlinden, AG, Jarvelin, M-R, Rice, K, Radke, D, Salomaa, V, van Dijk, KWillems, Boerwinkle, E, Vasan, RS, Ferrucci, L, Gibson, QD, Bandinelli, S, Snieder, H, Boomsma, DI, Xiao, X, Campbell, H, Hayward, C, Pramstaller, PP, van Duijn, CM, Peltonen, L, Psaty, BM, Gudnason, V, Ridker, PM, Homuth, G, Koenig, W, Ballantyne, CM, Witteman, JCM, Benjamin, EJ, Perola, M, Chasman, DI
JournalCirculation
Volume123
Issue7
Pagination731-8
Date Published2011 Feb 22
ISSN1524-4539
KeywordsBiomarkers, C-Reactive Protein, Cardiovascular Diseases, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Risk Factors, Vasculitis
Abstract<p><b>BACKGROUND: </b>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.</p><p><b>METHODS AND RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p>
DOI10.1161/CIRCULATIONAHA.110.948570
Alternate JournalCirculation
PubMed ID21300955
PubMed Central IDPMC3147232
Grant ListCZB/4/710 / / Chief Scientist Office / United Kingdom
G0801056 / / Medical Research Council / United Kingdom
HL043851 / HL / NHLBI NIH HHS / United States
Z01 AG000015-50 / AG / NIA NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
G20234 / / Biotechnology and Biological Sciences Research Council / United Kingdom
GR069224 / / Wellcome Trust / United Kingdom
N01-HC-55022 / HC / NHLBI NIH HHS / United States
1R01 AG032098-01A1 / AG / NIA NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
N01-AG-12109 / AG / NIA NIH HHS / United States
MC_U127561128 / / Medical Research Council / United Kingdom
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC 25195 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
G0500539 / / Medical Research Council / United Kingdom
AG028321 / AG / NIA NIH HHS / United States
CA047988 / CA / NCI NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
/ / Intramural NIH HHS / United States
N01-HC-35129 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
P30 DK072488 / DK / NIDDK NIH HHS / United States
M01RR00425 / RR / NCRR NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01 HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01 HC-15103 / HC / NHLBI NIH HHS / United States
HL064753 / HL / NHLBI NIH HHS / United States
HL076784 / HL / NHLBI NIH HHS / United States
5R01 HL087679-02 / HL / NHLBI NIH HHS / United States
5R01 MH63706:02 / MH / NIMH NIH HHS / United States
N01-AG-12100 / AG / NIA NIH HHS / United States
PG/05/117 / / British Heart Foundation / United Kingdom
1RL1 MH083268-01 / MH / NIMH NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-45133 / HC / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
/ / Chief Scientist Office / United Kingdom
068545/Z/02 / / Wellcome Trust / United Kingdom
U01 HL072515 / HL / NHLBI NIH HHS / United States
1S10 RR163736-01A1 / RR / NCRR NIH HHS / United States
N02-HL-64278 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01 AG62103 / AG / NIA NIH HHS / United States
G0000934 / / Medical Research Council / United Kingdom
N01 AG62106 / AG / NIA NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
G0600705 / / Medical Research Council / United Kingdom

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