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Epigenome-wide association study of incident type 2 diabetes in a British population : EPIC-Norfolk study

Cardona, Alexia (author)
University of Cambridge
Day, Felix R. (author)
University of Cambridge
Perry, John R.B. (author)
University of Cambridge
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Loh, Marie (author)
National University of Singapore,Imperial College London,Agency for Science, Technology and Research (A*STAR)
Chu, Audrey Y. (author)
National Heart Lung and Blood Institute
Lehne, Benjamin (author)
Imperial College London
Paul, Dirk S. (author)
University of Cambridge
Lotta, Luca A. (author)
University of Cambridge
Stewart, Isobel D. (author)
University of Cambridge
Kerrison, Nicola D. (author)
University of Cambridge
Scott, Robert A. (author)
University of Cambridge
Khaw, Kay Tee (author)
University of Cambridge
Forouhi, Nita G. (author)
University of Cambridge
Langenberg, Claudia (author)
University of Cambridge
Liu, Chunyu (author)
National Heart Lung and Blood Institute,Boston University
Mendelson, Michael M. (author)
National Heart Lung and Blood Institute,Boston University,Boston Children's Hospital
Levy, Daniel (author)
National Heart Lung and Blood Institute
Beck, Stephan (author)
University College London,UCL Cancer Institute
Leslie, R. David (author)
Queen Mary University
Dupuis, Josée (author)
Boston University
Meigs, James B. (author)
Broad Institute,Massachusetts General Hospital,Harvard University
Kooner, Jaspal S. (author)
Imperial College London,Imperial College Healthcare NHS Trust,Ealing Hospital
Pihlajamäki, Jussi (author)
Kuopio University Hospital,University of Eastern Finland
Vaag, Allan (author)
AstraZeneca, Sweden
Perfilyev, Alexander (author)
Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
Ling, Charlotte (author)
Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
Hivert, Marie France (author)
Harvard University,Massachusetts General Hospital
Chambers, John C. (author)
Imperial College Healthcare NHS Trust,Ealing Hospital,Imperial College London,Nanyang Technological University
Wareham, Nicholas J. (author)
University of Cambridge
Ong, Ken K. (author)
University of Cambridge
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 (creator_code:org_t)
2019-09-10
2019
English 12 s.
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:12, s. 2315-2326
Related links:
http://dx.doi.org/10...
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https://diabetes.dia...
https://lup.lub.lu.s...
https://doi.org/10.2...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Epigenetic 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 populationbased 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 obesityrelated 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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