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Genome-Wide Analysis in Over 1 Million Individuals of European Ancestry Yields Improved Polygenic Risk Scores for Blood Pressure Traits Publisher Pubmed



Keaton JM1, 2 ; Kamali Z3, 4 ; Xie T3 ; Vaez A3, 4 ; Williams A1 ; Goleva SB1 ; Ani A3, 4 ; Evangelou E5, 6, 7 ; Hellwege JN8, 9, 10 ; Yengo L11 ; Young WJ12, 13 ; Traylor M12, 14 ; Giri A2, 15 ; Zheng Z11, 16 Show All Authors
Authors
  1. Keaton JM1, 2
  2. Kamali Z3, 4
  3. Xie T3
  4. Vaez A3, 4
  5. Williams A1
  6. Goleva SB1
  7. Ani A3, 4
  8. Evangelou E5, 6, 7
  9. Hellwege JN8, 9, 10
  10. Yengo L11
  11. Young WJ12, 13
  12. Traylor M12, 14
  13. Giri A2, 15
  14. Zheng Z11, 16
  15. Zeng J11
  16. Chasman DI17, 18
  17. Morris AP19
  18. Caulfield MJ12, 20
  19. Hwang SJ21, 22
  20. Kooner JS23
  21. Conen D24
  22. Attia JR25
  23. Morrison AC26
  24. Loos RJF27, 28, 29
  25. Kristiansson K30
  26. Schmidt R31
  27. Hicks AA32, 33
  28. Pramstaller PP32, 33
  29. Nelson CP34, 35
  30. Samani NJ33, 34, 35
  31. Risch L35, 36, 37
  32. Gyllensten U38
  33. Melander O38, 39, 40
  34. Riese H41
  35. Wilson JF42, 43
  36. Campbell H42
  37. Rich SS44
  38. Psaty BM45
  39. Lu Y46
  40. Rotter JI47
  41. Guo X47
  42. Rice KM48
  43. Vollenweider P49
  44. Sundstrom J50, 51
  45. Langenberg C52, 53, 54
  46. Tobin MD55, 56
  47. Giedraitis V57
  48. Luan J52
  49. Tuomilehto J30, 58, 59
  50. Kutalik Z59, 60, 61
  51. Ripatti S61, 62, 63
  52. Salomaa V30
  53. Girotto G64, 65
  54. Trompet S66, 67
  55. Jukema JW67, 68
  56. Van Der Harst P68, 69, 70
  57. Ridker PM17, 18
  58. Giulianini F17
  59. Vitart V43
  60. Goel A71, 72
  61. Watkins H71, 72
  62. Harris SE73
  63. Deary IJ73
  64. Van Der Most PJ3
  65. Oldehinkel AJ74
  66. Keavney BD75, 76
  67. Hayward C43, 77
  68. Campbell A77, 78
  69. Boehnke M79
  70. Scott LJ79
  71. Boutin T43
  72. Mamasoula C80
  73. Jarvelin MR81, 82, 83
  74. Peters A84, 85
  75. Gieger C86
  76. Lakatta EG87
  77. Cucca F88
  78. Hui J89, 90
  79. Knekt P91
  80. Enroth S92
  81. De Borst MH92, 93
  82. Polasek O93, 94, 95
  83. Concas MP65
  84. Catamo E65
  85. Cocca M65
  86. Ligao R96
  87. Hofer E97, 98
  88. Schmidt H99
  89. Spedicati B64
  90. Waldenberger M85, 86, 100
  91. Strachan DP101
  92. Laan M102
  93. Teumer A103, 104
  94. Dorr M104, 105
  95. Gudnason V106, 107
  96. Cook JP108
  97. Ruggiero D109, 110
  98. Kolcic I95, 111
  99. Boerwinkle E26, 112
  100. Traglia M113
  101. Lehtimaki T113, 114, 115
  102. Raitakari OT115, 116, 117
  103. Johnson AD21, 118
  104. Newtoncheh C16, 119
  105. Brown MJ12
  106. Dominiczak AF120
  107. Sever PJ121
  108. Poulter N122
  109. Chambers JC122, 123
  110. Elosua R124, 125, 126
  111. Siscovick D127
  112. Esko T128
  113. Metspalu A128
  114. Strawbridge RJ129, 130, 131
  115. Laakso M132, 133
  116. Hamsten A131
  117. Hottenga JJ134
  118. De Geus E134, 135
  119. Morris AD136, 137
  120. Palmer CNA138
  121. Nolte IM3
  122. Milaneschi Y139
  123. Marten J77
  124. Wright A77
  125. Zeggini E140, 141
  126. Howson JMM14, 142
  127. Odonnell CJ143
  128. Spector T144
  129. Nalls MA145, 146, 147
  130. Simonsick EM148
  131. Liu Y149
  132. Van Duijn CM150
  133. Butterworth AS141, 142, 151, 152, 153, 154
  134. Danesh JN141, 142, 151, 152, 153, 154, 155
  135. Menni C156
  136. Wareham NJ52
  137. Khaw KT157
  138. Sun YV158, 159
  139. Wilson PWF160, 164
  140. Cho K161, 162, 163
  141. Visscher PM11
  142. Denny JC1
  143. Munroe PB12, 20
  144. Warren HR12, 20
  145. Zeggini E140, 141
  146. Ruggiero D109, 110
  147. Levy D21, 117
  148. Edwards TL2
  149. Snieder H3
Show Affiliations
Authors Affiliations
  1. 1. Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
  2. 2. Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
  3. 3. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  4. 4. Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
  6. 6. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
  7. 7. Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Ioannina, Greece
  8. 8. Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
  9. 9. Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, United States
  10. 10. Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, United States
  11. 11. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
  12. 12. Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
  13. 13. Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS Trust, London, United Kingdom
  14. 14. Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, United Kingdom
  15. 15. Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, United States
  16. 16. Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, United States
  17. 17. Division of Preventive Medicine Brigham and Women’s Hospital, Boston, MA, United States
  18. 18. Harvard Medical School, Boston, MA, United States
  19. 19. Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, United Kingdom
  20. 20. NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
  21. 21. Population Sciences Branch, NHLBI Framingham Heart Study, Framingham, MA, United States
  22. 22. Department of Biostatistics, Boston University, Boston, MA, United States
  23. 23. National Heart and Lung Institute, Imperial College London, London, United Kingdom
  24. 24. Population Health Research Institute, McMaster University, Hamilton, ON, Canada
  25. 25. Faculty of Health and Medicine, University of Newcastle, New Lambton Heights, Newcastle, NSW, Australia
  26. 26. Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, United States
  27. 27. The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
  28. 28. The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
  29. 29. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  30. 30. Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
  31. 31. Department of Neurology/Medical University Graz, Graz, Austria
  32. 32. Institute for Biomedicine, Eurac Research, Bolzano, Italy
  33. 33. University of Lubeck, Lubeck, Germany
  34. 34. Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
  35. 35. NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom
  36. 36. Faculty of Medical Sciences, Private University of the Principality of Liechtenstein, Triesen, Liechtenstein
  37. 37. Department of Laboratory Medicine, Dr. Risch Anstalt, Vaduz, Liechtenstein
  38. 38. Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  39. 39. Department of Clinical Sciences Malmo, Lund University, Malmo, Sweden
  40. 40. Department of Internal Medicine, Skane University Hospital, Malmo, Sweden
  41. 41. Interdisciplinary Center Psychopathology and Emotional Regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  42. 42. Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom
  43. 43. MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom
  44. 44. Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States
  45. 45. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, WA, United States
  46. 46. Vanderbilt Genetic Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
  47. 47. The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States
  48. 48. Department of Biostatistics, University of Washington, Seattle, WA, United States
  49. 49. Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
  50. 50. Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  51. 51. The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia
  52. 52. MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom
  53. 53. Computational Medicine, Berlin Institute of Health (BIH) at Charite - Universitatsmedizin Berlin, Berlin, Germany
  54. 54. Precision Healthcare University Research Institute, Queen Mary University of London, London, United Kingdom
  55. 55. Department of Health Sciences, University of Leicester, Leicester, United Kingdom
  56. 56. Leicester NIHR Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
  57. 57. Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
  58. 58. Department of Public Health, University of Helsinki, Helsinki, Finland
  59. 59. Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
  60. 60. Center for Primary Care and Public Health (Unisante), University of Lausanne, Lausanne, Switzerland
  61. 61. Swiss Institute of Bioinformatics, Lausanne, Switzerland
  62. 62. Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
  63. 63. Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  64. 64. Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy
  65. 65. Institute for Maternal and Child Health - IRCCS, Burlo Garofolo, Trieste, Italy
  66. 66. Department Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
  67. 67. Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands
  68. 68. Netherlands Heart Institute, Utrecht, Netherlands
  69. 69. Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands
  70. 70. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  71. 71. Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
  72. 72. Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
  73. 73. Lothian Birth Cohorts Group, Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom
  74. 74. Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  75. 75. Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
  76. 76. Manchester Heart Institute, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
  77. 77. Centre for Genomic and Experimental Medicine, IGC, University of Edinburgh, Edinburgh, United Kingdom
  78. 78. Usher Institute, University of Edinburgh, Edinburgh, United Kingdom
  79. 79. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States
  80. 80. Population Health Sciences Institute, Newcastle University, Newcastle, United Kingdom
  81. 81. Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom
  82. 82. Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
  83. 83. Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland
  84. 84. Institute of Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
  85. 85. Lehrstuhl fur Epidemiologie, Institut fur Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-Maximilians-Universitat Munchen, Neuherberg, Germany
  86. 86. Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
  87. 87. Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States
  88. 88. Institute of Genetic and Biomedical Research, National Research Council (CNR), Monserrato, Italy
  89. 89. Busselton Population Medical Research Institute, Perth, WA, Australia
  90. 90. School of Population and Global Health, The University of Western Australia, Nedlands, WA, Australia
  91. 91. Population Health Unit, Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
  92. 92. Department of Immunology, Genetics, and Pathology, Biomedical Center, Science for Life Laboratory (SciLifeLab) Uppsala, Uppsala University, Uppsala, Sweden
  93. 93. Department of Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
  94. 94. University of Split School of Medicine, Split, Croatia
  95. 95. Algebra University College, Zagreb, Croatia
  96. 96. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
  97. 97. Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria
  98. 98. Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
  99. 99. Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria
  100. 100. German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
  101. 101. Population Health Sciences Institute St George’s, University of London, London, United Kingdom
  102. 102. Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
  103. 103. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
  104. 104. DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
  105. 105. Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
  106. 106. Icelandic Heart Association, Kopavogur, Iceland
  107. 107. Faculty of Medicine, University of Iceland, Kopavogur, Iceland
  108. 108. Department of Health Data Science, University of Liverpool, Liverpool, United Kingdom
  109. 109. IRCCS Neuromed, Pozzilli, Italy
  110. 110. Institute of Genetics and Biophysics - ‘A. Buzzati-Traverso’, National Research Council of Italy, Naples, Italy
  111. 111. Department of Public Health, University of Split School of Medicine, Split, Croatia
  112. 112. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, United States
  113. 113. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
  114. 114. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
  115. 115. Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  116. 116. Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
  117. 117. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
  118. 118. The Framingham Heart Study, Framingham, MA, United States
  119. 119. Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
  120. 120. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
  121. 121. International Centre for Circulatory Health, Imperial College London, London, United Kingdom
  122. 122. School of Public Health, Imperial College London, London, United Kingdom
  123. 123. Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore
  124. 124. Hospital del Mar Research Institute (IMIM), Barcelona, Spain
  125. 125. CIBER Enfermedades Cardiovasculares (CIBERCV), Barcelona, Spain
  126. 126. Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain
  127. 127. New York Academy of Medicine, New York, NY, United States
  128. 128. Institute of Genomics, University of Tartu, Tartu, Estonia
  129. 129. Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom
  130. 130. Health Data Research UK, Glasgow, United Kingdom
  131. 131. Division of Cardiovascular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  132. 132. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
  133. 133. Kuopio University Hospital, Kuopio, Finland
  134. 134. Department of Biological Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit, Amsterdam, Netherlands
  135. 135. Amsterdam Public Health Research Institute, Amsterdam University Medical Centre, Amsterdam, Netherlands
  136. 136. Data Science, University of Edinburgh, Edinburgh, United Kingdom
  137. 137. Health Data Research UK, London, United Kingdom
  138. 138. Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom
  139. 139. Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Public Health Research Institute, Amsterdam, Netherlands
  140. 140. Institute of Translational Genomics, Helmholtz Zentrum Munchen – German Research Center for Environmental Health, Neuherberg, Germany
  141. 141. Technical University of Munich (TUM) and Klinikum Rechts der Isar, TUM School of Medicine, Munich, Germany
  142. 142. British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
  143. 143. VA Boston Healthcare System, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
  144. 144. Department of Twin Research, King’s College London, London, United Kingdom
  145. 145. Center for Alzheimer’s and Related Dementias, NIA/NINDS, NIH, Bethesda, MD, United States
  146. 146. Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD, United States
  147. 147. DataTecnica LLC, Washington, DC, United States
  148. 148. Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States
  149. 149. Division of Cardiology, Duke University School of Medicine, Durham, NC, United States
  150. 150. Nuffield Department of Population Health, Big Data Institute, University of Oxford, Oxford, United Kingdom
  151. 151. British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, United Kingdom
  152. 152. Health Data Research UK Cambridge, University of Cambridge, Wellcome Genome Campus, Cambridge, United Kingdom
  153. 153. Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
  154. 154. National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, United Kingdom
  155. 155. Department of Human Genetics, The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
  156. 156. Department of Twin Research and Genetic Epidemiology, London, United Kingdom
  157. 157. Department of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
  158. 158. Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, United States
  159. 159. VA Atlanta Healthcare System, Decatur, GA, United States
  160. 160. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, United States
  161. 161. Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United States
  162. 162. Department of Medicine, Harvard Medical School, Boston, MA, United States
  163. 163. Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, United States
  164. 164. Emory Clinical Cardiovascular Research Institute, Atlanta, GA, United States

Source: Nature Genetics Published:2024


Abstract

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10−8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5–18.2 mmHg, P = 2.22 × 10−126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54–9.70; P = 4.13 × 10−44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781–0.801) to 0.826 (95% CI, 0.817–0.836, ∆AUROC, 0.035, P = 1.98 × 10−34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research. © The Author(s) 2024.
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