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dc.contributor.authorCardona, A
dc.contributor.authorDay, FR
dc.contributor.authorPerry, JRB
dc.contributor.authorLoh, M
dc.contributor.authorChu, AY
dc.contributor.authorLehne, B
dc.contributor.authorPaul, DS
dc.contributor.authorLotta, LA
dc.contributor.authorStewart, ID
dc.contributor.authorKerrison, ND
dc.contributor.authorScott, RA
dc.contributor.authorKhaw, KT
dc.contributor.authorForouhi, NG
dc.contributor.authorLangenberg, C
dc.contributor.authorLiu, C
dc.contributor.authorMendelson, MM
dc.contributor.authorLevy, D
dc.contributor.authorBeck, S
dc.contributor.authorLeslie, RD
dc.contributor.authorDupuis, J
dc.contributor.authoret al. incl. Pihlajamäki, J
dc.date.accessioned2020-01-14T11:28:22Z
dc.date.available2020-01-14T11:28:22Z
dc.date.issued2019
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/7933
dc.description.abstractEpigenetic changes may contribute substantially to risks of diseases of aging. Previous studies reported seven methylation variable positions (MVPs) robustly associated with incident type 2 diabetes mellitus (T2DM). However, their causal roles in T2DM are unclear. In an incident T2DM case-cohort study nested within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort, we used whole blood DNA collected at baseline, up to 11 years before T2DM onset, to investigate the role of methylation in the etiology of T2DM. We identified 15 novel MVPs with robust associations with incident T2DM and robustly confirmed three MVPs identified previously (near to TXNIP, ABCG1, and SREBF1). All 18 MVPs showed directionally consistent associations with incident and prevalent T2DM in independent studies. Further conditional analyses suggested that the identified epigenetic signals appear related to T2DM via glucose and obesity-related pathways acting before the collection of baseline samples. We integrated genome-wide genetic data to identify methylation-associated quantitative trait loci robustly associated with 16 of the 18 MVPs and found one MVP, cg00574958 at CPT1A, with a possible direct causal role in T2DM. None of the implicated genes were previously highlighted by genetic association studies, suggesting that DNA methylation studies may reveal novel biological mechanisms involved in tissue responses to glycemia.
dc.language.isoenglanti
dc.publisherAmerican Diabetes Association
dc.relation.ispartofseriesDiabetes
dc.relation.urihttp://dx.doi.org/10.2337/db18-0290
dc.rightsAll rights reserved
dc.titleEpigenome-Wide Association Study of Incident Type 2 Diabetes in a British Population: EPIC-Norfolk Study
dc.description.versionfinal draft
dc.contributor.departmentSchool of Medicine / Clinical Nutrition
uef.solecris.id65145710en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© American Diabetes Association
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7-HEALTH/279143/EU/Identification of epigenetic markers underlying increased risk of T2D in South Asians/EPI-MIGRANT
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/H2020-EU.3.1.3./643774/EU/Family-based intervention to improve healthy lifestyle and prevent Type 2 Diabetes amongst South Asians with central obesity and prediabetes/iHealth-T2D
dc.relation.doi10.2337/db18-0290
dc.description.reviewstatuspeerReviewed
dc.format.pagerange2315-2326
dc.relation.issn0012-1797
dc.relation.issue12
dc.relation.volume68
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessEi


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