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dc.contributor.authorLigthart, Symenen
dc.contributor.authorMarzi, Carolaen
dc.contributor.authorAslibekyan, Stellaen
dc.contributor.authorMendelson, Michael Men
dc.contributor.authorConneely, Karen Nen
dc.contributor.authorTanaka, Toshikoen
dc.contributor.authorColicino, Elenaen
dc.contributor.authorWaite, Lindsay Len
dc.contributor.authorJoehanes, Robyen
dc.contributor.authorGuan, Weihuaen
dc.contributor.authorBrody, Jennifer Aen
dc.contributor.authorElks, Cathyen
dc.contributor.authorMarioni, Riccardoen
dc.contributor.authorJhun, Min Aen
dc.contributor.authorAgha, Golarehen
dc.contributor.authorBressler, Janen
dc.contributor.authorWard-Caviness, Cavin Ken
dc.contributor.authorChen, Brian Hen
dc.contributor.authorHuan, Tianxiaoen
dc.contributor.authorBakulski, Kellyen
dc.contributor.authorSalfati, Elias Len
dc.contributor.authorWHI-EMPC, Investigatorsen
dc.contributor.authorFiorito, Giovannien
dc.contributor.authorCHARGE, epigenetics of Coronary Heart Diseaseen
dc.contributor.authorWahl, Simoneen
dc.contributor.authorSchramm, Katharinaen
dc.contributor.authorSha, Jinen
dc.contributor.authorHernandez, Dena Gen
dc.contributor.authorJust, Allan Cen
dc.contributor.authorSmith, Jennifer Aen
dc.contributor.authorSotoodehnia, Nonaen
dc.contributor.authorPilling, Luke Cen
dc.contributor.authorPankow, James Sen
dc.contributor.authorTsao, Phil Sen
dc.contributor.authorLiu, Chunyuen
dc.contributor.authorZhao, Weien
dc.contributor.authorGuarrera, Simonettaen
dc.contributor.authorMichopoulos, Vasiliki Jen
dc.contributor.authorSmith, Alicia Ken
dc.contributor.authorPeters, Marjolein Jen
dc.contributor.authorMelzer, Daviden
dc.contributor.authorVokonas, Pantelen
dc.contributor.authorFornage, Myriamen
dc.contributor.authorProkisch, Holgeren
dc.contributor.authorBis, Joshua Cen
dc.contributor.authorChu, Audrey Yen
dc.contributor.authorHerder, Christianen
dc.contributor.authorGrallert, Haralden
dc.contributor.authorYao, Chenen
dc.contributor.authorShah, Soniaen
dc.contributor.authorMcRae, Allan Fen
dc.contributor.authorLin, Honghuangen
dc.contributor.authorHorvath, Steveen
dc.contributor.authorFallin, Danieleen
dc.contributor.authorHofman, Alberten
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorWiggins, Kerri Len
dc.contributor.authorFeinberg, Andrew Pen
dc.contributor.authorStarr, John Men
dc.contributor.authorVisscher, Peter Men
dc.contributor.authorMurabito, Joanne Men
dc.contributor.authorKardia, Sharon LRen
dc.contributor.authorAbsher, Devin Men
dc.contributor.authorBinder, Elisabeth Ben
dc.contributor.authorSingleton, Andrew Ben
dc.contributor.authorBandinelli, Stefaniaen
dc.contributor.authorPeters, Annetteen
dc.contributor.authorWaldenberger, Melanieen
dc.contributor.authorMatullo, Giuseppeen
dc.contributor.authorSchwartz, Joel Den
dc.contributor.authorDemerath, Ellen Wen
dc.contributor.authorUitterlinden, André Gen
dc.contributor.authorvan, Meurs Joyce BJen
dc.contributor.authorFranco, Oscar Hen
dc.contributor.authorChen, Yii-Der Idaen
dc.contributor.authorLevy, Danielen
dc.contributor.authorTurner, Stephen Ten
dc.contributor.authorDeary, Ian Jen
dc.contributor.authorRessler, Kerry Jen
dc.contributor.authorDupuis, Joséeen
dc.contributor.authorFerrucci, Luigien
dc.contributor.authorOng, Kennethen
dc.contributor.authorAssimes, Themistocles Len
dc.contributor.authorBoerwinkle, Ericen
dc.contributor.authorKoenig, Wolfgangen
dc.contributor.authorArnett, Donna Ken
dc.contributor.authorBaccarelli, Andrea Aen
dc.contributor.authorBenjamin, Emelia Jen
dc.contributor.authorDehghan, Abbasen
dc.date.accessioned2017-02-06T12:18:59Z
dc.date.available2017-02-06T12:18:59Z
dc.date.issued2016-12-12en
dc.identifier.issn1474-7596
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/262314
dc.description.abstractBACKGROUND: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation. RESULTS: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10(-7)) in the discovery panel of European ancestry and replicated (P < 2.29 × 10(-4)) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (P < 8.47 × 10(-5)), ten (17%) CpG sites were associated with a nearby genetic variant (P < 2.50 × 10(-3)), and 51 (88%) were also associated with at least one related cardiometabolic entity (P < 9.58 × 10(-5)). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants. CONCLUSION: We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation.
dc.format.mediumElectronicen
dc.languageengen
dc.publisherBioMed Central
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectWHI-EMPC Investigatorsen
dc.subjectCHARGE epigenetics of Coronary Heart Diseaseen
dc.subjectHumansen
dc.subjectInflammationen
dc.subjectC-Reactive Proteinen
dc.subjectDNA Methylationen
dc.subjectGene Expressionen
dc.subjectEpigenesis, Geneticen
dc.subjectCpG Islandsen
dc.subjectQuantitative Trait Locien
dc.subjectAfrican Americansen
dc.subjectEuropean Continental Ancestry Groupen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectGenetic Variationen
dc.subjectGenome-Wide Association Studyen
dc.subjectNucleotide Motifsen
dc.titleDNA methylation signatures of chronic low-grade inflammation are associated with complex diseases.en
dc.typeArticle
prism.publicationDate2016en
prism.publicationNameGenome biologyen
prism.startingPage255
prism.volume17en
dc.identifier.doi10.17863/CAM.7572
dcterms.dateAccepted2016-11-30en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-12-12en
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidOng, Kenneth [0000-0003-4689-7530]
dc.identifier.eissn1474-760X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (unknown)
pubs.funder-project-idMRC (MC_UU_12015/2)
pubs.funder-project-idMRC (MC_PC_13048)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idMRC (via University of Exeter) (MR/M023095/1)
pubs.funder-project-idMRC (G0401527)
pubs.funder-project-idMedical Research Council (MC_EX_MR/L100002/1)
pubs.funder-project-idMedical Research Council (MC_U106179471)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International