6533b872fe1ef96bd12d4429
RESEARCH PRODUCT
Meta-Analysis of Genome-Wide Association Studies in >80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels
Kenneth RiceVeronique VitartToshiko TanakaStefania BandinelliJulie E. BuringOliver KussLuigi FerrucciBehrooz Z. AlizadehEric J.g. SijbrandsAnneli PoutaDörte RadkeBrenda W.j.h. PenninxGonneke WillemsenMaryam KavousiRussell P. TracyHenriette E. Meyer Zu SchwabedissenAaron R. FolsomDorret I. BoomsmaHarry CampbellXiuqing GuoKarl WerdanJosée DupuisJosée DupuisVilmundur GudnasonIgor RudanIgor RudanJacqueline C.m. WittemanMartin G. LarsonMartin G. LarsonJoão D. FontesJoão D. FontesPaul ScheetJohn F. KeaneyJohn F. KeaneyJoachim ThieryHarold SniederAlbert HofmanManuela UdaNiina PellikkaRobert Y.l. ZeeQuince GibsonChristie M. BallantyneDavid P. StrachanThor AspelundEric BoerwinkleCornelia M. Van DuijnSamuli RipattiKo Willems Van DijkBrad C. AstorIlja M. NolteCaroline HaywardAlex ParkerAntti-pekka SarinIda SurakkaPaul M. RidkerDavid S. SiscovickVeikko SalomaaSunita BadolaAndrew A. HicksBarbara ThorandMegan E. RudockJoshua C. BisDaniel I. ChasmanMaja BarbalićKarin Halina GreiserKarin Halina GreiserYongmei LiuAlexander TeumerRamachandran S. VasanJouko SundvallLauren YoungJack M. GuralnikRon C. HoogeveenNicole SoranzoNicholas L. SmithNelson B. FreimerGudny EiriksdottirPaul ElliottHenri WallaschofskiPeter HennemanJames F. WilsonMarkus PerolaBruce M. PsatyWolfgang KoenigLenore J. LaunerLeena PeltonenJoe CoreshMatthias NauckKim TsuiYalda JamshidiYalda JamshidiJens BaumertHenry VölzkeXiangjun XiaoAbbas DehghanChristian FuchsbergerSilvia NaitzaChristian GiegerRenate B. SchnabelJohannes KettunenLynda M. RoseAlbert V. SmithPeter P. PramstallerChen LuEmelia J. BenjaminAlan R. ShuldinerEco J. C. De GeusAimo RuokonenTamara B. HarrisDavid W. BatesWei SunJames S. PankowJerome I. RotterVijay NambiMarjo-riitta JaervelinGuillaume ParéDavid SchlessingerJennifer F. YamamotoJennifer F. YamamotoTim D. SpectorGeorg HomuthAndré G. Uitterlindensubject
Netherlands Twin Register (NTR)Genome-wide association studyDisease030204 cardiovascular system & hematology0302 clinical medicineDESIGNRisk FactorsFRAMINGHAMNETHERLANDS TWIN REGISTERgeneticsCRP GENE2. Zero hungerGenetics0303 health scienceseducation.field_of_studybiologyCOMMON VARIANTS3. Good healthHNF1AC-Reactive Proteinmyocardial infarctionCardiovascular DiseasesMeta-analysis/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingCardiology and Cardiovascular MedicineVasculitisPopulationArticle03 medical and health sciencesINFLAMMATIONSDG 3 - Good Health and Well-beingPhysiology (medical)/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_medicineHumansGenetic Predisposition to DiseaseCORONARY-HEART-DISEASEALPHA-GENEeducation030304 developmental biologyGenetic associationEPIDEMIOLOGIC APPLICATIONSgenome-wide association studyC-reactive proteinmedicine.diseasemeta-analysisinflammationbiology.proteinGENETICALLY ISOLATED POPULATIONMetabolic syndromeBiomarkersdescription
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 <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. 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-02-22 |