体質指数と肥満の悪影響に関するエピジェノーム全体の関連研究

Simone Wahl ^1,2,3, Alexander Drong ⁴, Benjamin Lehne ⁵

¹Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany.
²Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
³German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
⁴Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
⁵Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
⁶Institute of Health Sciences, P.O. Box 5000, FI-90014 University of Oulu, Finland.
⁷Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore 138648, Singapore.
⁸National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
⁹Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
¹⁰Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
¹¹Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK.
¹²Cancer Science Institute of Singapore, National University of Singapore, Singapore.
¹³Human Genetics Foundation-Torino, Torino, Italy.
¹⁴Medical Sciences Department, University of Torino, Torino, Italy.
¹⁵University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands.
¹⁶Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
¹⁷Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
¹⁸MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.
¹⁹UCLH Bariatric Centre for Weight Loss, Weight Management and Metabolic and Endocrine Surgery, University College London Hospitals, Ground Floor West Wing, 250 Euston Road, London NW1 2PG, UK.
²⁰Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.
²¹NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
²²Computational Medicine, School of Social and Community Medicine, University of Bristol and Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
²³EPIGET Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano and Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy.
²⁴Institute of Human Genetics, University Hospital Schleswig-Holstein, Kiel Campus, Kiel, Germany.
²⁵Centre for Haematology, Department of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
²⁶Molecular Epidemiology, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
²⁷Section of Infectious Diseases and Immunity, Department of Medicine, Imperial College London, London W12 0NN, UK.
²⁸High Throughput Genomics-Oxford Genomic Centre, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
²⁹Medical Department 1, University Hospital of the Technical University Dresden, Dresden, Germany.
³⁰Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
³¹Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
³²Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7PX, UK.
³³Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
³⁴Clinical and Experimental Surgery Department, Medical Research Institute, University of Alexandria, Hadara, Alexandria 21561, Egypt.
³⁵Department of Endocrinology, Diabetes and Obesity, Max Healthcare, New Delhi 110 017, India.
³⁶Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo 1628655, Japan.
³⁷Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale Tumori, Milano, Italy.
³⁸Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
³⁹Institute of Human Genetics, Technical University Munich, München, Germany.
⁴⁰DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
⁴¹Vascular Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London SW3 6LY, UK.
⁴²Dipartmento Di Medicina Clinica E Chirurgia Federio II University, Naples, Italy.
⁴³Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
⁴⁴Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Hospital Düsseldorf, Düsseldorf, Germany.
⁴⁵Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
⁴⁶Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, 751 44 Uppsala, Sweden.
⁴⁷Department of Visceral and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel Campus, Kiel, Germany.
⁴⁸Institute of Human Genetics, University Hospital of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany.
⁴⁹Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
⁵⁰Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
⁵¹Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
⁵²Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore.
⁵³Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore.
⁵⁴Cancer Registry and Histopathology Unit, 'Civile-M.P. Arezzo' Hospital, ASP 7, Ragusa, Italy.
⁵⁵Departments of Internal Medicine and Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
⁵⁶Epidemiology and Public Health, Imperial College London, London, UK.
⁵⁷Department of Public Health, Faculty of Medicine, University of Kelaniya, PO Box 6, Thalagolla Road, Ragama 11010, Sri Lanka.
⁵⁸The Institute of Cancer Research, Surrey SM2 5NG, UK.
⁵⁹Centre for Obesity Research, Rayne Institute, Department of Medicine, University College London, London WC1E 6JJ, UK.
⁶⁰William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
⁶¹Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁶²Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
⁶³University of Groningen, University Medical Center Groningen, Department of Cardiology, 9700 RB Groningen, The Netherlands.
⁶⁴Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, 3511 GC Utrecht, The Netherlands.
⁶⁵Hannover Unified Biobank, Hannover Medical School, Feodor-Lynen-Strasse 15, D-30625 Hanover, Germany.
⁶⁶Institute of Human Genetics, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hanover, Germany.
⁶⁷Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
⁶⁸Biocenter Oulu, P.O. Box 5000, Aapistie 5A, FI-90014 University of Oulu, Finland.
⁶⁹Center for Life Course Epidemiology, Faculty of Medicine, P.O. Box 5000, FI-90014 University of Oulu, Finland.
⁷⁰Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, PO Box 20, FI-90220 Oulu, 90029 OYS, Finland.
⁷¹Department of Pathology, National University Hospital, Singapore.
⁷²Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.
⁷³Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford OX3 7LJ, UK.
⁷⁴Imperial College Healthcare NHS Trust, London W12 0HS, UK.
⁷⁵Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

⁰Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany.

肥満はDNAメチル化の大幅な変化と関連しており,主に体重増加が原因です. これらのメチル化変化は2型糖尿病の将来的な発症を予測する.

科学分野

ゲノミクス
代謝健康
エピジェネティクス

背景

肥満は世界で15億人に影響を及ぼし 2型糖尿病や心血管疾患のリスクを高めています
肥満と代謝や炎症疾患を関連付けるメカニズムは完全に理解されていません
肥満は遺伝子発現の重要なレギュラーであるDNAメチル化に影響を与える可能性があります.

研究の目的

体質指数 (BMI) とDNAメチル化との関係を調査する.
メチル化変化が肥満の原因か結果かを判断する.
BMIに関連したメチル化変化の機能的影響と2型糖尿病に対するその予測的価値を探求する.

主な方法

10,261個のサンプルで,BMIに関連した位置を特定するためのエピジェノーム全体の関連研究 (EWAS).
遺伝的関連分析で因果関係が確認される
機能的ゲノム濃縮分析と遺伝子発現プロフィール
2型糖尿病におけるメチル化の予測値を評価するための予測分析

主要な成果

187の遺伝的位置がBMIと関連しており DNAのメチル化が広範囲に広がっていることを示しています
これらのメチル化変化は主に肥満の結果であることが示されています.
機能的なゲノム領域でメチル化位置が濃縮され,脂質代謝,基板輸送,炎症経路における遺伝子発現と関連している.
DNAメチル化障害が将来の2型糖尿病の発症を予測することが確認された (RR=SD増加あたり2. 3).

結論

肥満は,DNAメチル化における顕著で広範な変化と関連しています.
これらのメチル化変化は肥満の結果であり,重要な代謝および炎症経路に関連しています.
肥満の影響を受けたDNAメチル化パターンは,2型糖尿病の将来のリスクを予測し,新しい予防戦略の可能性を秘めています.

体質指数と肥満の悪影響に関するエピジェノーム全体の関連研究

まとめ

科学分野

背景

研究の目的

主な方法

主要な成果

結論

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体質指数と肥満の悪影響に関するエピジェノーム全体の関連研究

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まとめ

科学分野

背景

研究 の 目的

主な方法

主要な成果

結論

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研究の目的

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