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, John C., Loh, Marie, Lehne, Benjamin, Drong, Alexander, Kriebel, Jennifer, Motta, Valeria, Wahl, Simone, Elliott, Hannah R., Rota, Federica, Scott, William R., Zhang, Weihua, Tan, Sian-Tsung, Campanella, Gianluca, Chadeau-Hyam, Marc, Yengo, Loic, Richmond, Rebecca C., Adamowicz-Brice, Martyna, Afzal, Uzma, Bozaoglu, Kiymet, Mok, Zuan Yu, Ng, Hong Kiat, Pattou, Francois, Prokisch, Holger, Rozario, Michelle Ann, Tarantini, Letizia, Abbott, James, Ala-Korpela, Mika, Albetti, Benedetta, Ammerpohl, Ole, Bertazzi, Pier Alberto, Blancher, Christine, Caiazzo, Robert, Danesh, John, Gaunt, Tom R., de Lusignan, Simon, Gieger, Christian, Illig, Thomas, Jha, Sujeet, Jones, Simon, Jowett, Jeremy, Kangas, Antti J., Kasturiratne, Anuradhani, Kato, Norihiro, Kotea, Navaratnam, Kowlessur, Sudhir, Pitkaeniemi, Janne, Punjabi, Prakash, Saleheen, Danish, Schafmayer, Clemens, Soininen, Pasi, Tai, E-Shyong, Thorand, Barbara, Tuomilehto, Jaakko, Wickremasinghe, Ananda Rajitha, Kyrtopoulos, Soterios A., Aitman, Timothy J., Herder, Christian, Hampe, Jochen, Cauchi, Stephane, Relton, Caroline L., Froguel, Philippe, Soong, Richie, Vineis, Paolo, Jarvelin, Marjo-Riitta, Scott, James, Grallert, Harald, Bollati, Valentina, Elliott, Paul, McCarthy, Mark I. and Kooner, Jaspal S. (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 and Endocrinology, 3 7: 526-534. doi:10.1016/S2213-8587(15)00127-8

Author Chambers, John C.
Loh, Marie
Lehne, Benjamin
Drong, Alexander
Kriebel, Jennifer
Motta, Valeria
Wahl, Simone
Elliott, Hannah R.
Rota, Federica
Scott, William R.
Zhang, Weihua
Tan, Sian-Tsung
Campanella, Gianluca
Chadeau-Hyam, Marc
Yengo, Loic
Richmond, Rebecca C.
Adamowicz-Brice, Martyna
Afzal, Uzma
Bozaoglu, Kiymet
Mok, Zuan Yu
Ng, Hong Kiat
Pattou, Francois
Prokisch, Holger
Rozario, Michelle Ann
Tarantini, Letizia
Abbott, James
Ala-Korpela, Mika
Albetti, Benedetta
Ammerpohl, Ole
Bertazzi, Pier Alberto
Blancher, Christine
Caiazzo, Robert
Danesh, John
Gaunt, Tom R.
de Lusignan, Simon
Gieger, Christian
Illig, Thomas
Jha, Sujeet
Jones, Simon
Jowett, Jeremy
Kangas, Antti J.
Kasturiratne, Anuradhani
Kato, Norihiro
Kotea, Navaratnam
Kowlessur, Sudhir
Pitkaeniemi, Janne
Punjabi, Prakash
Saleheen, Danish
Schafmayer, Clemens
Soininen, Pasi
Tai, E-Shyong
Thorand, Barbara
Tuomilehto, Jaakko
Wickremasinghe, Ananda Rajitha
Kyrtopoulos, Soterios A.
Aitman, Timothy J.
Herder, Christian
Hampe, Jochen
Cauchi, Stephane
Relton, Caroline L.
Froguel, Philippe
Soong, Richie
Vineis, Paolo
Jarvelin, Marjo-Riitta
Scott, James
Grallert, Harald
Bollati, Valentina
Elliott, Paul
McCarthy, Mark I.
Kooner, Jaspal S.
Title 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
Journal name Lancet Diabetes and Endocrinology   Check publisher's open access policy
ISSN 2213-8595
Publication date 2015-07-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/S2213-8587(15)00127-8
Open Access Status Not yet assessed
Volume 3
Issue 7
Start page 526
End page 534
Total pages 9
Place of publication London, United Kingdom
Publisher Lancet Publishing Group
Language eng
Subject 2724 Internal Medicine
2712 Endocrinology, Diabetes and Metabolism
1310 Endocrinology
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.
Keyword Endocrinology & Metabolism
Endocrinology & Metabolism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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