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A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure
Authors:Yun J. Sung  Thomas W. Winkler  Lisa de las Fuentes  Amy R. Bentley  Michael R. Brown  Aldi T. Kraja  Karen Schwander  Ioanna Ntalla  Xiuqing Guo  Nora Franceschini  Yingchang Lu  Ching-Yu Cheng  Xueling Sim  Dina Vojinovic  Jonathan Marten  Solomon K. Musani  Changwei Li  Mary F. Feitosa  Daniel I. Chasman
Affiliation:1. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA;2. Department of Genetic Epidemiology, University of Regensburg, Regensburg 93051, Germany;3. Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO 63110, USA;4. Center for Research on Genomics and Global Health, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA;5. Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, TX 77030, USA;6. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA;7. William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London, London EC1M 6BQ, UK;8. Genomic Outcomes, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA 90502, USA;9. Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC 27514, USA;10. Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, NY 10029, USA;11. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore 169856, Singapore;12. Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore 169857, Singapore;13. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 117597, Singapore;14. Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore 117549, Singapore;15. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands;16. Medical Research Council Human Genetics Unit, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK;17. Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39213, USA;18. Department of Epidemiology and Biostatistics, University of Giorgia at Athens College of Public Health, Athens, GA 30602, USA;19. Section of Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark;20. Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;21. Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA;22. Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2300RC, the Netherlands;23. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;24. Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA;25. Centre de Bioinformatique Biostatistique et Biologie Integrative (C3BI), Institut Pasteur, Paris 75015, France;26. Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, WA 98101, USA;27. Genome Institute of Singapore, Agency for Science Technology and Research, Singapore 138672, Singapore;28. Division of Biostatistical Sciences, Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA;29. Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA 02114, USA;30. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;31. Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA;32. Icelandic Heart Association, Kopavogur 201, Iceland;33. Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland;34. Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA;35. Department of Public Health Sciences, Loyola University Chicago, Maywood, IL 60153, USA;36. NIHR Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK;37. School of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA;38. Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA;39. Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan;40. Department of Biostatistics, University of Washington, Seattle, WA 98105, USA;41. Estonian Genome Center, University of Tartu, Tartu 51010, Estonia;42. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, the Netherlands;43. CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille 59000, France;44. Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore;45. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden;46. Department of Medical Sciences, University of Trieste, Trieste 34137, Italy;47. Department of Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA;48. Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02215, USA;49. Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire OX3 9DU, UK;50. Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK;51. Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh EH8 9JZ, UK;52. Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh EH4 2XU, UK;53. Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, RS 96020220, Brazil;54. Lab Genetics and Molecular Cardiology, Department of Cardiology, Heart Institute, University of Sao Paulo, Sao Paulo, Brazil;55. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA;56. Department of Clinical Physiology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33014, Finland;57. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland;58. Department of Public Health, University of Kelaniya, Ragama, Sri Lanka;59. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany;60. Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany;61. Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden;62. Department of Medical Research, Taichung Veterans General Hospital, Department of Social Work, Tunghai University, Taichung 40705, Taiwan;63. Department of Opthalmology, Taichung Veterans General Hospital, Taichung 40705, Taiwan;64. MRC Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UK;65. Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona JMAAW15, Jamaica;66. Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China;67. Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK;68. NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK;69. Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio 70100, Finland;70. Taub Institute for Research on Alzheimer disease and the Aging Brain, Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA;71. Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan;72. School of Medicine, National Yang-ming University, Taipei, Taiwan;73. School of Medicine, National Defense Medical Center, Taipei, Taiwan;74. Institute of Medical Technology, National Chung-Hsing University, Taichung 40705, Taiwan;75. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio 70210, Finland;76. Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo 1628655, Japan;77. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Skåne 205 02, Sweden;78. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA;79. Institute for Social Research, Research Center for Group Dynamics, University of Michigan, Ann Arbor, MI 48104, USA;80. Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz Arndt University Greifswald, Greifswald 17487, Germany;81. DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald 17475, Germany;82. Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37203, USA;83. General Internal Medicine, GeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;84. Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK;85. Department of Cardiology, Ealing Hospital, Middlesex UB1 3HW, UK;86. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;87. Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY 10032, USA;88. Human Genetics Center, The University of Texas School of Public Health, Houston, TX 77030, USA;89. Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, TX 77030, USA;90. Cardiovascular Health Research Unit, Medicine, University of Washington, Seattle, WA 98101, USA;91. Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;92. Sleep Medicine and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA 02115, USA;93. Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK;94. Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;95. Centre for Brain Research, Indian Institute of Schience, Bangalore 560012, India;96. The Danish Aging Research Center, Institute of Public Health, University of Southern Denmark, Odense, Denmark;97. Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA;98. Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK;99. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden 2300RC, the Netherlands;100. Department of Medicine, University of Kelaniya, Ragama, Sri Lanka;101. Inserm U1219 Neuroepidemiology, University of Bordeaux, Bordeaux, France;102. Department of Neurology, University Hospital, Bordeaux, France;103. Boston University School of Medicine, Boston, MA 02118, USA;104. Department of Internal Medicine B, University Medicine Greifswald, Greifswald 17475, Germany;105. Department of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA;106. Department of Family Medicine and Epidemiology, Alpert Medical School of Brown University, Providence, RI 02860, USA;107. Division of Cardiology, Department of Specialties of Medicine, Geneva University Hospital, Geneva 1211, Switzerland;108. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece;109. Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI 48104, USA;110. Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem 91120, Israel;111. MRC-PHE Centre for Environment and Health, Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, UK;112. Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;113. Department of Psychology, The University of Edinburgh, Edinburgh EH8 9JZ, UK;114. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, MD 20892, USA;115. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA;116. Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA;117. University of Eastern Finland, Institute of Biomedicine, Kuopio 70211, Finland;118. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore;119. Khoo Teck Puat – National University Children’s Medical Institute, National University Health System, Singapore 119228, Singapore;120. Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku 108-8639, Japan;121. MedStar Health Research Institute, Hyattsville, MD 20782, USA;122. Center for Clinical and Translational Sciences and Department of Medicine, Georgetown-Howard Universities, Washington, DC 20057, USA;123. Cardiovascular Genetics, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84108, USA;124. Weill Cornell Medicine in Qatar, Doha, Qatar;125. Hebrew SeniorLife, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02131, USA;126. Framingham Heart Study, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20982, USA;127. Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita 5650871, Japan;128. Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita 5650871, Japan;129. Epidemiology, Department of Occupational and Environmental Medicine Program, University of Washington, Seattle, WA 98105, USA;130. Department of Biochemistry, National University of Singapore, Singapore 117596, Singapore;131. Duke-NUS Medical School, Singapore 169857, Singapore;132. Department of Health, National Institute for Health and Welfare, Helsinki 00271, Finland;133. Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki 00029, Finland;134. Fred Hutchinson Cancer Research Center, University of Washington School of Public Health, Seattle, WA 98109, USA;135. Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan;136. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland;137. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205, USA;138. Lifelines cohort study, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, the Netherlands;139. WHI CCC, Fred Hutchinson Cancer Research Center, Seattle, WA 98115, USA;140. Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA;141. Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research 138648, Singapore;142. Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany;143. Institute of Human Genetics, Technische Universität München, Munich 80333, Germany;144. Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan;145. Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK;146. Geriatrics, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA;147. Mathematical and Statistical Computing Laboratory, Center for Information Technology, NIH, Bethesda, MD 20892, USA;148. The Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen AB25 2ZD, UK;149. Data Tecnica International, Glen Echo, MD 20812, USA;150. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA;151. Department of Epidemiology, Colorado School of Public Health, Aurora, CO 80045, USA;152. Department of Medicine, University of Ibadan, Ibadan, Nigeria;153. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK;154. Internal Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA;155. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA;156. Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN 55454, USA;157. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Neuherberg 85764, Germany;158. Faculty of Medicine, University of Split, Split, Croatia;159. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20521, Finland;160. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland;161. Department of Biobank Research, Umeå University, Umeå, Västerbotten 901 87, Sweden;162. Medical Genetics, IRCCS Burlo, Garofolo 34137, Italy;163. Department of Epidemiology and Medicine, University of Iowa, Iowa City, IA 52242, USA;164. Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK;165. Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany;166. National Heart and Lung Institute, Imperial College London, London W12 0NN, UK;167. Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA;168. International Centre for Circulatory Health, Imperial College London, London W2 1PG, UK;169. Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh EH8 9JZ, UK;170. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany;171. Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Munich 81377, Germany;172. Department of Genetics, Stanford University, Stanford, CA 94305, USA;173. Life Sciences Institute, National University of Singapore, Singapore, Singapore 117456, Singapore;174. NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore 117456, Singapore;175. Department of Statistics and Applied Probability, National University of Singapore, Singapore 117546, Singapore;176. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands;177. Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Capital Medical University, Beijing, China 100730, China;178. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;179. Jackson Heart Study, Department of Public Health, Jackson State University, Jackson, MS 39213, USA;180. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA;181. Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA;182. Behavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA;183. Broad Institute of the Massachusetts Institute of Technology and Harvard University, Boston, MA 02142, USA;184. Harvard T.H. Chan School of Public Health, Department of Nutrition, Harvard University, Boston, MA 02115, USA;185. Department of Public Health & Clinical Medicine, Umeå University, Umeå, Västerbotten 901 85, Sweden;186. Division of Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA;187. Department of Genomics of Common Disease, Imperial College London, London W12 0NN, UK;188. Division Experimental Genetics, Sidra, Doha 26999, Qatar;189. German Center for Diabetes Research (DZD e.V.), Neuherberg 85764, Germany;190. Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taipei 11490, Taiwan;191. Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, Mannheim 68167, Germany;192. Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland;193. Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Lifes Sciences, University of Tampere, Tampere 33014, Finland;194. Cardiovascular Center, Taichung Veterans General Hospital, Taichung 40705, Taiwan;195. Department of Medicine, China Medical University, Taichung 40705, Taiwan;196. Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, the Netherlands;197. Genetics, Harvard Medical School, Boston, MA 02115, USA;198. Institute of Physiology, University Medicine Greifswald, Greifswald 17495, Germany;199. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, the Netherlands;200. Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA;201. Sticht Center for Health Aging and Alzheimer’s Prevention, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA;202. Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA;203. Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA;204. Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;205. Cardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA 98101, USA;206. Kaiser Permanente Washington, Health Research Institute, Seattle, WA 98101, USA;207. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore;208. Dean’s Office, University of Kentucky College of Public Health, Lexington, KY 40536, USA;209. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden 2300RC, the Netherlands;210. Cardiology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA;211. Icahn School of Medicine at Mount Sinai, The Mindich Child Health and Development Institute, New York, NY 10029, USA;212. Genomic Outcomes, Department of Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA 90502, USA;213. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA;214. Division of Biostatistics, Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90032, USA;215. NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London EC1M 6BQ, UK
Abstract:
Keywords:GWAS  GxE interactions  lifestyle  blood pressure  multi-ancestry  smoking
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