Journal
LANCET DIABETES & ENDOCRINOLOGY
Volume 3, Issue 7, Pages 526-534Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S2213-8587(15)00127-8
Keywords
-
Categories
Funding
- European Union
- UK National Institute for Health Research
- Wellcome Trust
- UK Medical Research Council
- Action on Hearing Loss
- UK Biotechnology and Biological Sciences Research Council
- Oak Foundation
- Economic and Social Research Council
- Helmholtz Zentrum Munchen
- German Research Center for Environmental Health
- German Federal Ministry of Education and Research
- German Center for Diabetes Research
- Munich Center for Health Sciences
- Ministry of Science and Research of the State of North Rhine-Westphalia
- German Federal Ministry of Health
- Biotechnology and Biological Sciences Research Council [BB/I025263/1] Funding Source: researchfish
- British Heart Foundation [RG/08/014/24067] Funding Source: researchfish
- Medical Research Council [MR/K002414/1, G0601966, G0700931, MC_UU_12013/2, MR/L01341X/1, MR/L003120/1, MC_UU_12013/8, MC_U120061454] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10099, ACF-2009-18-005, NF-SI-0611-10136, RP-PG-0407-10371, NF-SI-0512-10165] Funding Source: researchfish
- RNID [G51] Funding Source: researchfish
- BBSRC [BB/I025751/1, BB/I025263/1] Funding Source: UKRI
- MRC [MR/L01341X/1, MR/K002414/1, MR/L003120/1, MC_UU_12013/8, MC_UU_12013/2, MC_U120061454, G0601966, G0700931] Funding Source: UKRI
- National Institutes of Health Research (NIHR) [RP-PG-0407-10371] Funding Source: National Institutes of Health Research (NIHR)
Ask authors/readers for more resources
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 x 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 x 10(-17)) for ABCG1, 0.94 (0.92-0.95; p=4.2 x 10(-11)) for PHOSPHO1, 0.94 (0.92-0.96; p= 1.4 x 10(-9)) for SOCS3, 1.07 (1.04-1.09; p = 2.1 x 10(- 10)) for SREBF1, and 0.92 (0.90-0.94; p= 1.2 x 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 13.51, 95% CI 2.79-4.42; p= 1.3 x 10(-26)), and was independent of established risk factors. Methylation score was higher among Indian Asians than Europeans (p = 1 x 10(-34)). Interpretation DNA methylation might provide new insights into the pathways underlying type 2 diabetes and off er new opportunities for risk stratification and prevention of type 2 diabetes among Indian Asians.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available