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Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study.

Chambers, JC, Loh, M, Lehne, B, Drong, A, Kriebel, J, Motta, V, Wahl, S, Elliott, HR, Rota, F, Scott, WR, Zhang, W, Tan, ST, Campanella, G, Chadeau-Hyam, M, Yengo, L, Richmond, RC, Adamowicz-Brice, M, Afzal, U, Bozaoglu, K, Mok, ZY, Ng, HK, Pattou, F, Prokisch, H, Rozario, MA, Tarantini, L, Abbott, J, Ala-Korpela, M, Albetti, B, Ammerpohl, O, Bertazzi, PA, Blancher, C, Caiazzo, R, Danesh, J, Gaunt, TR, de Lusignan, S, Gieger, C, Illig, T, Jha, S, Jones, S, Jowett, J, Kangas, AJ, Kasturiratne, A, Kato, N, Kotea, N, Kowlessur, S, Pitkäniemi, J, Punjabi, P, Saleheen, D, Schafmayer, C, Soininen, P, Tai, ES, Thorand, B, Tuomilehto, J, Wickremasinghe, AR, Kyrtopoulos, SA, Aitman, TJ, Herder, C, Hampe, J, Cauchi, S, Relton, CL, Froguel, P, Soong, R, Vineis, P, Jarvelin, MR, Scott, J, Grallert, H, Bollati, V, Elliott, P, McCarthy, MI and Kooner, JS (2015) Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study. Lancet Diabetes Endocrinol, 3 (7). pp. 526-534.

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Abstract

BACKGROUND: Indian Asians, who make up a quarter of the world's population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes. METHODS: We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p<1 × 10(-7). We compared methylation levels between Indian Asian and European controls without type 2 diabetes at baseline to estimate the potential contribution of DNA methylation to increased risk of future type 2 diabetes incidence among Indian Asians. FINDINGS: 1608 (11·9%) of 13 535 Indian Asians and 306 (4·3%) of 7066 Europeans developed type 2 diabetes over a mean of 8·5 years (SD 1·8) of follow-up. The age-adjusted and sex-adjusted incidence of type 2 diabetes was 3·1 times (95% CI 2·8-3·6; p<0·0001) higher among Indian Asians than among Europeans, and remained 2·5 times (2·1-2·9; p<0·0001) higher after adjustment for adiposity, physical activity, family history of type 2 diabetes, and baseline glycaemic measures. The mean absolute difference in methylation level between type 2 diabetes cases and controls ranged from 0·5% (SD 0·1) to 1·1% (0·2). Methylation markers at five loci were associated with future type 2 diabetes incidence; the relative risk per 1% increase in methylation was 1·09 (95% CI 1·07-1·11; p=1·3 × 10(-17)) for ABCG1, 0·94 (0·92-0·95; p=4·2 × 10(-11)) for PHOSPHO1, 0·94 (0·92-0·96; p=1·4 × 10(-9)) for SOCS3, 1·07 (1·04-1·09; p=2·1 × 10(-10)) for SREBF1, and 0·92 (0·90-0·94; p=1·2 × 10(-17)) for TXNIP. A methylation score combining results for the five loci was associated with future type 2 diabetes incidence (relative risk quartile 4 vs quartile 1 3·51, 95% CI 2·79-4·42; p=1·3 × 10(-26)), and was independent of established risk factors. Methylation score was higher among Indian Asians than Europeans (p=1 × 10(-34)). INTERPRETATION: DNA methylation might provide new insights into the pathways underlying type 2 diabetes and offer new opportunities for risk stratification and prevention of type 2 diabetes among Indian Asians. FUNDING: The European Union, the UK National Institute for Health Research, the Wellcome Trust, the UK Medical Research Council, Action on Hearing Loss, the UK Biotechnology and Biological Sciences Research Council, the Oak Foundation, the Economic and Social Research Council, Helmholtz Zentrum Munchen, the German Research Center for Environmental Health, the German Federal Ministry of Education and Research, the German Center for Diabetes Research, the Munich Center for Health Sciences, the Ministry of Science and Research of the State of North Rhine-Westphalia, and the German Federal Ministry of Health.

Item Type: Article
Subjects : Health Care Management
Divisions : Faculty of Arts and Social Sciences > Surrey Business School
Authors :
AuthorsEmailORCID
Chambers, JCUNSPECIFIEDUNSPECIFIED
Loh, MUNSPECIFIEDUNSPECIFIED
Lehne, BUNSPECIFIEDUNSPECIFIED
Drong, AUNSPECIFIEDUNSPECIFIED
Kriebel, JUNSPECIFIEDUNSPECIFIED
Motta, VUNSPECIFIEDUNSPECIFIED
Wahl, SUNSPECIFIEDUNSPECIFIED
Elliott, HRUNSPECIFIEDUNSPECIFIED
Rota, FUNSPECIFIEDUNSPECIFIED
Scott, WRUNSPECIFIEDUNSPECIFIED
Zhang, WUNSPECIFIEDUNSPECIFIED
Tan, STUNSPECIFIEDUNSPECIFIED
Campanella, GUNSPECIFIEDUNSPECIFIED
Chadeau-Hyam, MUNSPECIFIEDUNSPECIFIED
Yengo, LUNSPECIFIEDUNSPECIFIED
Richmond, RCUNSPECIFIEDUNSPECIFIED
Adamowicz-Brice, MUNSPECIFIEDUNSPECIFIED
Afzal, UUNSPECIFIEDUNSPECIFIED
Bozaoglu, KUNSPECIFIEDUNSPECIFIED
Mok, ZYUNSPECIFIEDUNSPECIFIED
Ng, HKUNSPECIFIEDUNSPECIFIED
Pattou, FUNSPECIFIEDUNSPECIFIED
Prokisch, HUNSPECIFIEDUNSPECIFIED
Rozario, MAUNSPECIFIEDUNSPECIFIED
Tarantini, LUNSPECIFIEDUNSPECIFIED
Abbott, JUNSPECIFIEDUNSPECIFIED
Ala-Korpela, MUNSPECIFIEDUNSPECIFIED
Albetti, BUNSPECIFIEDUNSPECIFIED
Ammerpohl, OUNSPECIFIEDUNSPECIFIED
Bertazzi, PAUNSPECIFIEDUNSPECIFIED
Blancher, CUNSPECIFIEDUNSPECIFIED
Caiazzo, RUNSPECIFIEDUNSPECIFIED
Danesh, JUNSPECIFIEDUNSPECIFIED
Gaunt, TRUNSPECIFIEDUNSPECIFIED
de Lusignan, SUNSPECIFIEDUNSPECIFIED
Gieger, CUNSPECIFIEDUNSPECIFIED
Illig, TUNSPECIFIEDUNSPECIFIED
Jha, SUNSPECIFIEDUNSPECIFIED
Jones, SUNSPECIFIEDUNSPECIFIED
Jowett, JUNSPECIFIEDUNSPECIFIED
Kangas, AJUNSPECIFIEDUNSPECIFIED
Kasturiratne, AUNSPECIFIEDUNSPECIFIED
Kato, NUNSPECIFIEDUNSPECIFIED
Kotea, NUNSPECIFIEDUNSPECIFIED
Kowlessur, SUNSPECIFIEDUNSPECIFIED
Pitkäniemi, JUNSPECIFIEDUNSPECIFIED
Punjabi, PUNSPECIFIEDUNSPECIFIED
Saleheen, DUNSPECIFIEDUNSPECIFIED
Schafmayer, CUNSPECIFIEDUNSPECIFIED
Soininen, PUNSPECIFIEDUNSPECIFIED
Tai, ESUNSPECIFIEDUNSPECIFIED
Thorand, BUNSPECIFIEDUNSPECIFIED
Tuomilehto, JUNSPECIFIEDUNSPECIFIED
Wickremasinghe, ARUNSPECIFIEDUNSPECIFIED
Kyrtopoulos, SAUNSPECIFIEDUNSPECIFIED
Aitman, TJUNSPECIFIEDUNSPECIFIED
Herder, CUNSPECIFIEDUNSPECIFIED
Hampe, JUNSPECIFIEDUNSPECIFIED
Cauchi, SUNSPECIFIEDUNSPECIFIED
Relton, CLUNSPECIFIEDUNSPECIFIED
Froguel, PUNSPECIFIEDUNSPECIFIED
Soong, RUNSPECIFIEDUNSPECIFIED
Vineis, PUNSPECIFIEDUNSPECIFIED
Jarvelin, MRUNSPECIFIEDUNSPECIFIED
Scott, JUNSPECIFIEDUNSPECIFIED
Grallert, HUNSPECIFIEDUNSPECIFIED
Bollati, VUNSPECIFIEDUNSPECIFIED
Elliott, PUNSPECIFIEDUNSPECIFIED
McCarthy, MIUNSPECIFIEDUNSPECIFIED
Kooner, JSUNSPECIFIEDUNSPECIFIED
Date : July 2015
Identification Number : 10.1016/S2213-8587(15)00127-8
Copyright Disclaimer : © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 08 Jun 2016 17:25
Last Modified : 26 Jul 2016 10:09
URI: http://epubs.surrey.ac.uk/id/eprint/809828

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