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An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis.

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dc.contributor.authorLiu, Jun
dc.contributor.authorCarnero-Montoro, Elena
dc.contributor.authorvan Dongen, Jenny
dc.contributor.authorLent, Samantha
dc.contributor.authorNedeljkovic, Ivana
dc.contributor.authorLigthart, Symen
dc.contributor.authorTsai, Pei-Chien
dc.contributor.authorMartin, Tiphaine C
dc.contributor.authorMandaviya, Pooja R
dc.contributor.authorJansen, Rick
dc.contributor.authorPeters, Marjolein J
dc.contributor.authorDuijts, Liesbeth
dc.contributor.authorJaddoe, Vincent W V
dc.contributor.authorTiemeier, Henning
dc.contributor.authorFelix, Janine F
dc.contributor.authorWillemsen, Gonneke
dc.contributor.authorde Geus, Eco J C
dc.contributor.authorChu, Audrey Y
dc.contributor.authorLevy, Daniel
dc.contributor.authorHwang, Shih-Jen
dc.contributor.authorBressler, Jan
dc.contributor.authorGondalia, Rahul
dc.contributor.authorSalfati, Elias L
dc.contributor.authorHerder, Christian
dc.contributor.authorHidalgo, Bertha A
dc.contributor.authorTanaka, Toshiko
dc.contributor.authorMoore, Ann Zenobia
dc.contributor.authorLemaitre, Rozenn N
dc.contributor.authorJhun, Min A
dc.contributor.authorSmith, Jennifer A
dc.contributor.authorSotoodehnia, Nona
dc.contributor.authorBandinelli, Stefania
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorArnett, Donna K
dc.contributor.authorGrallert, Harald
dc.contributor.authorAssimes, Themistocles L
dc.contributor.authorHou, Lifang
dc.contributor.authorBaccarelli, Andrea
dc.contributor.authorWhitsel, Eric A
dc.contributor.authorvan Dijk, Ko Willems
dc.contributor.authorAmin, Najaf
dc.contributor.authorUitterlinden, André G
dc.contributor.authorSijbrands, Eric J G
dc.contributor.authorFranco, Oscar H
dc.contributor.authorDehghan, Abbas
dc.contributor.authorSpector, Tim D
dc.contributor.authorDupuis, Josée
dc.contributor.authorHivert, Marie-France
dc.contributor.authorRotter, Jerome I
dc.contributor.authorMeigs, James B
dc.contributor.authorPankow, James S
dc.contributor.authorvan Meurs, Joyce B J
dc.contributor.authorIsaacs, Aaron
dc.contributor.authorBoomsma, Dorret I
dc.contributor.authorBell, Jordana T
dc.contributor.authorDemirkan, Ayşe
dc.contributor.authorvan Duijn, Cornelia M
dc.date.accessioned2023-01-25T13:34:54Z
dc.date.available2023-01-25T13:34:54Z
dc.date.issued2019-06-13
dc.description.abstractDespite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.
dc.identifier.doi10.1038/s41467-019-10487-4
dc.identifier.essn2041-1723
dc.identifier.pmcPMC6565679
dc.identifier.pmid31197173
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565679/pdf
dc.identifier.unpaywallURLhttps://www.nature.com/articles/s41467-019-10487-4.pdf
dc.identifier.urihttp://hdl.handle.net/10668/14112
dc.issue.number1
dc.journal.titleNature communications
dc.journal.titleabbreviationNat Commun
dc.language.isoen
dc.organizationCentro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica e Investigación Oncológica-GENYO
dc.page.number2581
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshComputer Simulation
dc.subject.meshCpG Islands
dc.subject.meshDNA Methylation
dc.subject.meshDiabetes Mellitus, Type 2
dc.subject.meshEpigenesis, Genetic
dc.subject.meshEpigenomics
dc.subject.meshFemale
dc.subject.meshGene Expression Profiling
dc.subject.meshGene Expression Regulation
dc.subject.meshGenome-Wide Association Study
dc.subject.meshGlucose
dc.subject.meshHomeostasis
dc.subject.meshHumans
dc.subject.meshInsulin
dc.subject.meshMale
dc.subject.meshMetabolic Networks and Pathways
dc.subject.meshMiddle Aged
dc.subject.meshObesity
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshYoung Adult
dc.titleAn integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number10
dspace.entity.typePublication

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