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Genetic Architecture of the Inflammatory Bowel Diseases Across East Asian and European Ancestries Publisher Pubmed



Liu Z1 ; Liu R2, 3 ; Gao H1 ; Jung S4 ; Gao X1, 69 ; Sun R1 ; Liu X5 ; Kim Y4 ; Lee HS4 ; Kawai Y6 ; Nagasaki M7, 8 ; Umeno J9 ; Tokunaga K6 ; Kinouchi Y10 Show All Authors
Authors
  1. Liu Z1
  2. Liu R2, 3
  3. Gao H1
  4. Jung S4
  5. Gao X1, 69
  6. Sun R1
  7. Liu X5
  8. Kim Y4
  9. Lee HS4
  10. Kawai Y6
  11. Nagasaki M7, 8
  12. Umeno J9
  13. Tokunaga K6
  14. Kinouchi Y10
  15. Masamune A11
  16. Shi W12
  17. Shen C12
  18. Guo Z3
  19. Yuan K2, 3
  20. Abreu M25
  21. Achkar JP26
  22. Andersen V27
  23. Bernstein C28
  24. Brant SR29
  25. Bujanda L30
  26. Ng SC31
  27. Denson LA32
  28. Duerr RH33
  29. Ferguson LR34
  30. Franchimont D35
  31. Franke A36
  32. Gearry R37
  33. Hakonarson H38
  34. Halfvarson J39
  35. Heller C40
  36. Julia A41
  37. Kelsen J38
  38. Khalili H42
  39. Kugathasan S43
  40. Kupcinskas J44
  41. Latiano A45
  42. Louis E46
  43. Malekzadeh R47
  44. Mccauley JL48
  45. Moran C49
  46. Okou D43
  47. Orchard T50
  48. Palotie A2, 3, 21
  49. Parkes M51
  50. Pekow J52
  51. Potocnik U53
  52. Radfordsmith G54
  53. Rioux JD55
  54. Rogler G56
  55. Sands B57
  56. Silverberg M58
  57. Sokol H59
  58. Vermeire S60
  59. Weersma RK61
  60. Xavier RJ62
  61. Hu N63
  62. Cao Q64
  63. Wang Y65
  64. Miao Y66
  65. Zhang H67
  66. Lv X68
  67. Zhang H67
  68. Su J70
  69. Feng B71
  70. Zhao Y72
  71. Zhu L73
  72. Chen Y74
  73. Zhu L73
  74. Chen C76
  75. Wang Y65
  76. Wang Y65
  77. Pang Z79
  78. Chen Y74
  79. Zhang X81
  80. Li H82
  81. Yu Q83
  82. Ye M84
  83. Zhang S85
  84. Tang W86
  85. Wang M87
  86. Cao X88
  87. Zhu R89
  88. Zhou G90
  89. Bian Z91
  90. Guo X92
  91. Wu X93
  92. Liu J94
  93. Xu W95
  94. Li Y96
  95. Guo Q97
  96. Guo Z3
  97. Zhu S13
  98. Li D14
  99. Liu J94
  100. Ge T17, 18, 19
  101. Cho J20
  102. Daly MJ2, 21, 22
  103. Mcgovern DPB14
  104. Ye BD23
  105. Song K4
  106. Kakuta Y11
  107. Li M5
  108. Huang H2, 3, 24
Show Affiliations
Authors Affiliations
  1. 1. Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
  2. 2. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States
  3. 3. Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, United States
  4. 4. Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea
  5. 5. Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
  6. 6. Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, Japan
  7. 7. Human Biosciences Unit for the Top Global Course Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan
  8. 8. Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  9. 9. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  10. 10. Student Healthcare Center, Institute for Excellence in Higher Education, Tohoku University, Sendai, Japan
  11. 11. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
  12. 12. Digital Health China Technologies Corp Ltd., Beijing, China
  13. 13. Institute of Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
  14. 14. Widjaja Inflammatory Bowel Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States
  15. 15. Genome Institute of Singapore, Singapore, Singapore
  16. 16. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  17. 17. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
  18. 18. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
  19. 19. Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, United States
  20. 20. Icahn School of Medicine at Mount Sinai, New York, NY, United States
  21. 21. Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland
  22. 22. Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, United States
  23. 23. Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
  24. 24. Department of Medicine, Harvard Medical School, Boston, MA, United States
  25. 25. Division of Gastroenterology, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United States
  26. 26. Cleveland Clinic, Cleveland, OH, United States
  27. 27. Focused Research Unit for Molecular Diagnostic and Clinical Research, Hospital of Southern Jutland, Aabenraa, Denmark
  28. 28. University of Manitoba IBD Clinical and Research Centre, Winnipeg, MB, Canada
  29. 29. Rutgers University, New Brunswick, NJ, United States
  30. 30. Osakidetza-Basque Health Service, Bilbao, Spain
  31. 31. The Chinese University of Hong Kong, Hong Kong
  32. 32. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
  33. 33. Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
  34. 34. The University of Auckland, Auckland, New Zealand
  35. 35. Department of Gastroenterology, Erasme Hospital, Free University of Brussels, Brussels, Belgium
  36. 36. Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University of Kiel, Kiel, Germany
  37. 37. Department of Medicine, University of Otago, Christchurch, New Zealand
  38. 38. Children’s Hospital of Philadelphia, Philadelphia, PA, United States
  39. 39. Department of Gastroenterology, Faculty of Medicine and Health, Orebro University, Orebro, Sweden
  40. 40. Crohn’s & Colitis Foundation, New York, NY, United States
  41. 41. Rheumatology Research Group, Vall d’Hebron University Hospital, Barcelona, Spain
  42. 42. Massachusetts General Hospital Gastroenterology Unit, Boston, MA, United States
  43. 43. Emory University, Atlanta, GA, United States
  44. 44. Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
  45. 45. Fondazione IRCCS Casa Sollievo della Sofferenza, Gastroenterology Unit, San Giovanni Rotondo, Foggia, Italy
  46. 46. University of Liege, ULG, Liege, Belgium
  47. 47. DDRI, Tehran University of Medical Sciences, Tehran, Iran
  48. 48. John P. Hussman Institute for Human Genomics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United States
  49. 49. MassGeneral Hospital for Children, Boston, MA, United States
  50. 50. Imperial College London, London, United Kingdom
  51. 51. Addenborookes Hospital, Cambridge, United Kingdom
  52. 52. University of Chicago, Chicago, IL, United States
  53. 53. Faculty of Medicine, Center for Human Molecular Genetics and Pharmacogenomics, University of Maribor, Maribor, Slovenia
  54. 54. QIMR Berghofer MRI, Herston, QLD, Australia
  55. 55. Montreal Heart InstituteResearch Center, Montreal, QC, Canada
  56. 56. Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
  57. 57. Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
  58. 58. Mount Sinai Hospital, Toronto, ON, Canada
  59. 59. St Antoine Hospital, APHP, Paris, France
  60. 60. Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium
  61. 61. Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands
  62. 62. The Broad Institute of MIT and Harvard, Cambridge, MA, United States
  63. 63. Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
  64. 64. Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  65. 65. Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
  66. 66. Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
  67. 67. Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
  68. 68. Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
  69. 69. Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  70. 70. Department of Gastroenterology, Affiliated Zhongshan Hospital of Xiamen University, Xiamen, China
  71. 71. Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  72. 72. Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  73. 73. Department of Gastroenterology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
  74. 74. Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  75. 75. Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
  76. 76. Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  77. 77. Department of Gastroenterology, Datong Third People’s Hospital, Datong, China
  78. 78. Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
  79. 79. Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
  80. 80. Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  81. 81. Department of Gastroenterology, The East Branch of the Second Hospital of Hebei Medical University, Shijiazhuang, China
  82. 82. Department of Gastroenterology, The Second Hospital of Harbin Medical University, Harbin, China
  83. 83. Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
  84. 84. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
  85. 85. Department of Colorectal Surgery, Nanjing Hospital of TCM Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
  86. 86. Department of Gastroenterology, The Second Hospital of Soochow University, Suzhou, China
  87. 87. Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, China
  88. 88. Department of Gastroenterology, General Hospital, Tianjin Medical University, Tianjin, China
  89. 89. Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, China
  90. 90. Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining, China
  91. 91. Department of Gastroenterology, Nantong Third People’s Hospital, Nantong University, Nantong, China
  92. 92. Department of Gastroenterology, Shanxi Provincial People’s Hospital, Taiyuan, China
  93. 93. Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  94. 94. Department of Gastroenterology, First Hospital of Shanxi Medical University, Taiyuan, China
  95. 95. Department of Colorectal Surgery, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, China
  96. 96. Department of Gastroenterology, Bethune First Affiliated Hospital of Jilin University, Changchun, China
  97. 97. Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha, China
  98. 98. Department of Gastroenterology, Suzhou Hospital of Anhui Medical University, Suzhou, China

Source: Nature Genetics Published:2023


Abstract

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract with the following two subtypes: Crohn’s disease (CD) and ulcerative colitis (UC). To date, most IBD genetic associations were derived from individuals of European (EUR) ancestries. Here we report the largest IBD study of individuals of East Asian (EAS) ancestries, including 14,393 cases and 15,456 controls. We found 80 IBD loci in EAS alone and 320 when meta-analyzed with ~370,000 EUR individuals (~30,000 cases), among which 81 are new. EAS-enriched coding variants implicate many new IBD genes, including ADAP1 and GIT2. Although IBD genetic effects are generally consistent across ancestries, genetics underlying CD appears more ancestry dependent than UC, driven by allele frequency (NOD2) and effect (TNFSF15). We extended the IBD polygenic risk score (PRS) by incorporating both ancestries, greatly improving its accuracy and highlighting the importance of diversity for the equitable deployment of PRS. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.