Meta-analysis of epigenome-wide association studies of carotid intima-media thickness,European Journal of Epidemiology

当前位置： X-MOL 学术 › Eur. J. Epidemiol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness
European Journal of Epidemiology ( IF 7.7 ) Pub Date : 2021-06-06 , DOI: 10.1007/s10654-021-00759-z
Eliana Portilla-Fernández _{1,

2} , Shih-Jen Hwang _{3,

4} , Rory Wilson ₅ , Jane Maddock ₆ , W David Hill _{7,

8} , Alexander Teumer _{9,

10} , Pashupati P Mishra ₁₁ , Jennifer A Brody ₁₂ , Roby Joehanes ₄ , Symen Ligthart ₁ , Mohsen Ghanbari ₁ , Maryam Kavousi ₁ , Anton J M Roks ₂ , A H Jan Danser ₂ , Daniel Levy ₃ , Annette Peters _{5,

13,

14} , Sahar Ghasemi _{9,

10} , Ulf Schminke ₁₅ , Marcus Dörr _{10,

16} , Hans J Grabe ₁₇ , Terho Lehtimäki ₁₁ , Mika Kähönen ₁₈ , Mikko A Hurme ₁₉ , Traci M Bartz ₁₂ , Nona Sotoodehnia ₁₂ , Joshua C Bis ₁₂ , Joachim Thiery ₂₀ , Wolfgang Koenig _{21,

22,

23} , Ken K Ong ₂₄ , Jordana T Bell ₂₅ , Christine Meisinger _{26,

27} , Joanna M Wardlaw _{7,

28,

29,

30} , John M Starr ₇ , Jochen Seissler _{31,

32} , Cornelia Then _{31,

32} , Wolfgang Rathmann _{14,

33} , M Arfan Ikram ₁ , Bruce M Psaty _{12,

34,

35,

36} , Olli T Raitakari _{37,

38,

39} , Henry Völzke _{9,

10} , Ian J Deary _{7,

8} , Andrew Wong ₆ , Melanie Waldenberger _{5,

14} , Christopher J O'Donnell _{40,

41} , Abbas Dehghan _{1,

42,

43,

44}

Affiliation

Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Framingham Heart Study, Framingham, MA, USA.
Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, University College London, London, UK.
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.
Intitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Griefswald, Greifswald, Germany.
Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
German Center for Diabetes Research, Neuherberg, Germany.
Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Department of Microbiology and Immunology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital, Leipzig, Leipzig, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.
MRC Epidemiology Unit and Department of Paediatrics, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Independent Research Group, Clinical Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Ludwig-Maximilians-Universität München, UNIKA-T, Augsburg, Germany.
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Edinburgh Imaging, University of Edinburgh, Edinburgh, UK.
UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
Diabetes Zentrum, Medizinische Klinik und Poliklinik IV - Campus Innenstadt, Klinikum Der Ludwig-Maximilians-Universität München, Munich, Germany.
Clinical Cooperation Group Diabetes, Ludwig-Maximilians-Universität München and Helmholtz Zentrum München, Munich, Germany.
Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Department of Health Services, University of Washington, Seattle, WA, USA.
Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Cardiology Section and Center for Population Genomics, VA Boston Healthcare System, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, Room 157, Norfolk Place, St Mary's Campus, London, UK.
UK Dementia Research Institute at Imperial College London, London, UK.
MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10^–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

中文翻译：

颈动脉内膜中层厚度表观基因组关联研究的荟萃分析

颈总动脉内膜中层厚度 (cIMT) 是与缺血性中风和冠状动脉疾病 (CAD) 相关的亚临床动脉粥样硬化的指标。我们对 6400 个人的 cIMT 测量进行了横断面表观基因组范围关联研究 (EWAS)。应用孟德尔随机化分析来研究 DNA 甲基化在动脉粥样硬化心血管危险因素与 cIMT 或临床心血管疾病之间的联系中的潜在因果作用。CpG 站点 cg05575921 与发现面板中的cIMT（beta = −0.0264， p值 = 3.5 × 10 ^–8 ）相关，并在复制面板中复制（beta = −0.07， p值 = 0.005）。该 CpG 位于芳烃受体阻遏基因 ( AHRR )内含子 3 的 chr5:81649347 。我们的结果表明 cg05575921 的 DNA 甲基化可能在吸烟、cIMT 和中风之间的通路中。此外，在基于区域的分析中，确定了 34 个差异甲基化区域 (DMR)，其中ALOX12上游的 DMR显示与 cIMT 的关联最强（p值 = 1.4 × 10 ^–13）。总之，我们的研究表明 DNA 甲基化可能在心血管危险因素、cIMT 和临床心血管疾病之间的联系中发挥作用。

更新日期：2021-06-07

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11