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DNA methylation analysis identifies novel genetic loci associated with circulating fibrinogen levels in blood

dc.rights.licenseopenen_US
dc.contributor.authorHAHN, Julie
dc.contributor.authorBRESSLER, Jan
dc.contributor.authorDOMINGO-RELLOSO, Arce
dc.contributor.authorCHEN, Ming-Huei
dc.contributor.authorMCCARTNEY, Daniel L.
dc.contributor.authorTEUMER, Alexander
dc.contributor.authorVAN DONGEN, Jenny
dc.contributor.authorKLEBER, Marcus E.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorAISSI, Dylan
dc.contributor.authorSWENSON, Brenton R.
dc.contributor.authorYAO, Jie
dc.contributor.authorZHAO, Wei
dc.contributor.authorHUANG, Jian
dc.contributor.authorXIA, Yujing
dc.contributor.authorBROWN, Michael R.
dc.contributor.authorCOSTEIRA, Ricardo
dc.contributor.authorDE GEUS, Eco J. C.
dc.contributor.authorDELGADO, Graciela E.
dc.contributor.authorDOBSON, Dre'Von A.
dc.contributor.authorELLIOTT, Paul
dc.contributor.authorGRABE, Hans J.
dc.contributor.authorGUO, Xiuqing
dc.contributor.authorHARRIS, Sarah E.
dc.contributor.authorHUFFMAN, Jennifer E.
dc.contributor.authorKARDIA, Sharon L. R.
dc.contributor.authorLIU, Yongmei
dc.contributor.authorLORKOWSKI, Stefan
dc.contributor.authorMARIONI, Riccardo E.
dc.contributor.authorNAUCK, Matthias
dc.contributor.authorRATLIFF, Scott M.
dc.contributor.authorSABATER-LLEAL, Maria
dc.contributor.authorSPECTOR, Tim D.
dc.contributor.authorSUCHON, Pierre
dc.contributor.authorTAYLOR, Kent D.
dc.contributor.authorTHIBORD, Florian
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorWIGGINS, Kerri L.
dc.contributor.authorWILLEMSEN, Gonneke
dc.contributor.authorBELL, Jordana T.
dc.contributor.authorBOOMSMA, Dorret I.
dc.contributor.authorCOLE, Shelley A.
dc.contributor.authorCOX, Simon R.
dc.contributor.authorDEHGHAN, Abbas
dc.contributor.authorGREINACHER, Andreas
dc.contributor.authorHAACK, Karin
dc.contributor.authorMARZ, Winfried
dc.contributor.authorMORANGE, Pierre-Emmanuel
dc.contributor.authorROTTER, Jerome I.
dc.contributor.authorSOTOODEHNIA, Nona
dc.contributor.authorTELLEZ-PLAZA, Maria
dc.contributor.authorNAVAS-ACIEN, Ana
dc.contributor.authorSMITH, Jennifer A.
dc.contributor.authorJOHNSON, Andrew D.
dc.contributor.authorFORNAGE, Myriam
dc.contributor.authorSMITH, Nicholas L.
dc.contributor.authorWOLBERG, Alisa S.
dc.contributor.authorMORRISON, Alanna C.
dc.contributor.authorDE VRIES, Paul S.
dc.date.accessioned2023-02-22T09:28:42Z
dc.date.available2023-02-22T09:28:42Z
dc.date.issued2023-05
dc.identifier.issn1538-7836 (Electronic) 1538-7836 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/172054
dc.description.abstractEnBACKGROUND: Fibrinogen plays an essential role in blood coagulation and inflammation. Circulating fibrinogen levels may be determined by inter-individual differences in DNA methylation at CpG sites, and vice versa. METHODS: We performed an epigenome-wide association study (EWAS) of circulating fibrinogen levels in 18,037 White, Black, American Indian, and Hispanic participants representing 14 studies from the CHARGE consortium. Circulating leukocyte DNA methylation was measured in 12,904 participants using the Illumina 450K array, and in 5,133 participants using the EPIC array. Each study performed an EWAS of fibrinogen using linear mixed models adjusted for potential confounders. Study-specific results were combined using array-specific meta-analysis, followed by cross-replication of epigenome-wide significant associations. We compared models with and without C-reactive protein (CRP) adjustment to examine the role of inflammation. RESULTS: We identified 208 and 87 significant CpG sites associated with fibrinogen from the 450K (p-value<1.03×10(-7)) and EPIC arrays (p-value<5.78×10(-8)), respectively. There were 78 associations from the 450K array that replicated in the EPIC array and 26 vice versa. After accounting for the overlapping sites, there were 83 replicated CpG sites located in 61 loci, of which only 4 have been previously reported for fibrinogen. Examples of genes located near these CpG sites were SOCS3 and AIM2, which are involved in inflammatory pathways. The associations for all 83 replicated CpG sites were attenuated after CRP adjustment, although many remained significant. CONCLUSION: We identified 83 CpG sites associated with circulating fibrinogen levels. These associations are partially driven by inflammatory pathways shared by both fibrinogen and CRP.
dc.language.isoENen_US
dc.subject.enDNA methylation
dc.subject.enEpigenome-wide association study
dc.subject.enFibrinogen
dc.subject.enInflammation
dc.subject.enMendelian randomization
dc.title.enDNA methylation analysis identifies novel genetic loci associated with circulating fibrinogen levels in blood
dc.title.alternativeJ Thromb Haemosten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.jtha.2023.01.015en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed36716967en_US
bordeaux.journalJournal of Thrombosis and Haemostasisen_US
bordeaux.page1135-1147
bordeaux.volume21
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue5
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-04000185
hal.version1
hal.date.transferred2023-02-22T09:30:22Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
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