Impact of BMI and waist circumference on epigenome-wide DNA methylation and identification of epigenetic biomarkers in blood: an EWAS in multi-ethnic Asian individuals

Springer Science and Business Media LLC - 2021
Yuqing Chen1, Irfahan Kassam1, Suk Hiang Lau2, Jaspal S. Kooner3,4,5, Rory Wilson6, Annette Peters7,8, Juliane Winkelmann9,10,11,12, John C. Chambers5,3,4,13, Vincent Chow14, Chiea Chuen Khor15,16, Rob M van Dam17,1, Yik-Ying Teo1, Marie Loh18,19,13, Xueling Sim1
1Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
2Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
3Imperial College Healthcare NHS Trust, Imperial College London, London, UK
4MRC-PHE Centre for Environment and Health, Imperial College London, London, UK
5Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, Middlesex, UK
6Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Bavaria, Germany
7German Center for Cardiovascular Research, partner site Munich Heart Alliance, Munich, Germany
8Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
9Lehrstuhl für Neurogenetik, Technische Universität München, Munich, Germany
10Munich Cluster for Systems Neurology, Munich, Germany
11Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany
12Institute of Human Genetics, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany
13Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
14National University Health System Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
15Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
16Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
17Department of Nutrition and Department of Epidemiology, Harvard T.H. Chan, School of Public Health, Boston, USA
18Department of Epidemiology and Biostatistics, Imperial College London, London, UK
19National Skin Centre, Singapore, Singapore

Tóm tắt

Abstract Background The prevalence of obesity and its related chronic diseases have been increasing especially in Asian countries. Obesity-related genetic variants have been identified, but these explain little of the variation in BMI. Recent studies reported associations between DNA methylation and obesity, mostly in non-Asian populations. Methods We performed an epigenome-wide association study (EWAS) on general adiposity (body mass index, BMI) and abdominal adiposity (waist circumference, WC) in 409 multi-ethnic Asian individuals and replicated BMI and waist-associated DNA methylation CpGs identified in other populations. The cross-lagged panel model and Mendelian randomization were used to assess the temporal relationship between methylation and BMI. The temporal relationship between the identified CpGs and inflammation and metabolic markers was also examined. Results EWAS identified 116 DNA methylation CpGs independently associated with BMI and eight independently associated with WC at false discovery rate PFDR < 0.05 in 409 Asian samples. We replicated 110 BMI-associated CpGs previously reported in Europeans and identified six novel BMI-associated CpGs and two novel WC-associated CpGs. We observed high consistency in association direction of effect compared to studies in other populations. Causal relationship analyses indicated that BMI was more likely to be the cause of DNA methylation alteration, rather than the consequence. The causal analyses using BMI-associated methylation risk score also suggested that higher levels of the inflammation marker IL-6 were likely the consequence of methylation change. Conclusion Our study provides evidence of an association between obesity and DNA methylation in multi-ethnic Asians and suggests that obesity can drive methylation change. The results also suggested possible causal influence that obesity-related methylation changes might have on inflammation and lipoprotein levels.

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