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Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology Publisher Pubmed



Suzuki K1, 2, 3 ; Hatzikotoulas K4 ; Southam L4 ; Taylor HJ5, 6, 7 ; Yin X8, 9 ; Lorenz KM10, 11, 12 ; Mandla R13, 14 ; Huertachagoya A13 ; Melloni GEM15 ; Kanoni S16 ; Rayner NW4 ; Bocher O4 ; Arruda AL4, 17, 18 ; Sonehara K3, 19, 20, 21 Show All Authors
Authors
  1. Suzuki K1, 2, 3
  2. Hatzikotoulas K4
  3. Southam L4
  4. Taylor HJ5, 6, 7
  5. Yin X8, 9
  6. Lorenz KM10, 11, 12
  7. Mandla R13, 14
  8. Huertachagoya A13
  9. Melloni GEM15
  10. Kanoni S16
  11. Rayner NW4
  12. Bocher O4
  13. Arruda AL4, 17, 18
  14. Sonehara K3, 19, 20, 21
  15. Namba S3
  16. Lee SSK22
  17. Preuss MH22
  18. Petty LE23
  19. Schroeder P13, 14
  20. Vanderwerff B9
  21. Kals M24
  22. Bragg F25, 26
  23. Lin K25
  24. Guo X27
  25. Zhang W28, 29
  26. Yao J27
  27. Kim YJ30
  28. Graff M31
  29. Takeuchi F32
  30. Nano J33
  31. Lamri A34, 35
  32. Nakatochi M36
  33. Moon S30
  34. Scott RA37
  35. Cook JP38
  36. Lee JJ39
  37. Pan I40
  38. Taliun D9
  39. Parra EJ41
  40. Chai JF42
  41. Bielak LF43
  42. Tabara Y44
  43. Hai Y27
  44. Thorleifsson G45
  45. Grarup N46
  46. Sofer T47, 48, 49
  47. Wuttke M50
  48. Sarnowski C51
  49. Gieger C33, 52, 53
  50. Nousome D54
  51. Trompet S55, 56
  52. Kwak SH57
  53. Long J58
  54. Sun M59
  55. Tong L60
  56. Chen WM61
  57. Nongmaithem SS62
  58. Noordam R56
  59. Lim VJY42
  60. Tam CHT63, 64
  61. Joo YY65
  62. Chen CH68
  63. Raffield LM69
  64. Prins BP70
  65. Nicolas A71
  66. Yanek LR72
  67. Chen G73
  68. Brody JA74
  69. Kabagambe E58, 75
  70. An P76
  71. Xiang AH77
  72. Choi HS78
  73. Cade BE48, 79
  74. Tan J27
  75. Broadaway KA69
  76. Williamson A37, 80
  77. Kamali Z81, 82
  78. Cui J83
  79. Thangam M84
  80. Adair LS85
  81. Adeyemo A73
  82. Aguilarsalinas CA86
  83. Ahluwalia TS87, 88
  84. Anand SS34, 35, 89
  85. Bertoni A90
  86. Borkjensen J46
  87. Brandslund I91, 92
  88. Buchanan TA93
  89. Burant CF94
  90. Butterworth AS6, 95, 96, 97
  91. Canouil M98, 99
  92. Chan JCN63, 64, 100, 101
  93. Chang LC68
  94. Chee ML102
  95. Chen J103, 104
  96. Chen SH105
  97. Chen YT68
  98. Chen Z25, 26
  99. Chuang LM106, 107
  100. Cushman M108
  101. Danesh J6, 70, 95, 96, 97
  102. Das SK109
  103. De Silva HJ110
  104. Dedoussis G111
  105. Dimitrov L112
  106. Doumatey AP73
  107. Du S85, 113
  108. Duan Q69
  109. Eckardt KU114, 115
  110. Emery LS116
  111. Evans DS117
  112. Evans MK118
  113. Fischer K24, 119
  114. Floyd JS74
  115. Ford I120
  116. Franco OH121
  117. Frayling TM122
  118. Freedman BI123
  119. Genter P124
  120. Gerstein HC34, 35, 89
  121. Giedraitis V125
  122. Gonzalezvillalpando C126
  123. Gonzalezvillalpando ME126
  124. Gordonlarsen P85, 113
  125. Gross M127
  126. Guare LA128
  127. Hackinger S70
  128. Hakaste L129, 130
  129. Han S30
  130. Hattersley AT131
  131. Herder C52, 132, 133
  132. Horikoshi M134
  133. Howard AG113, 135
  134. Hsueh W136
  135. Huang M40, 137
  136. Huang W138
  137. Hung YJ139, 140
  138. Hwang MY30
  139. Hwu CM141, 142
  140. Ichihara S143
  141. Ikram MA121
  142. Ingelsson M125
  143. Islam MT144
  144. Isono M32
  145. Jang HM30
  146. Jasmine F60
  147. Jiang G63, 64
  148. Jonas JB145
  149. Jorgensen T146, 147, 148
  150. Kamanu FK15
  151. Kandeel FR149
  152. Kasturiratne A150
  153. Katsuya T151, 152
  154. Kaur V14
  155. Kawaguchi T44
  156. Keaton JM5, 58, 112
  157. Kho AN153, 154
  158. Khor CC155
  159. Kibriya MG60
  160. Kim DH156
  161. Kronenberg F157
  162. Kuusisto J158
  163. Lall K24
  164. Lange LA159
  165. Lee KM160, 161
  166. Lee MS162, 163
  167. Lee NR164
  168. Leong A165, 166
  169. Li L167, 168
  170. Li Y69
  171. Ligao R169
  172. Ligthart S121
  173. Lindgren CM170, 171, 172
  174. Linneberg A146, 173
  175. Liu CT174
  176. Liu J155, 175
  177. Locke AE176, 177, 300
  178. Louie T116
  179. Luan J37
  180. Luk AO63, 64
  181. Luo X178
  182. Lv J167, 168
  183. Lynch JA160, 161
  184. Lyssenko V179, 180
  185. Maeda S134, 181, 182
  186. Mamakou V183
  187. Mansuri SR62, 184
  188. Matsuda K185
  189. Meitinger T186, 187, 188
  190. Melander O84
  191. Metspalu A24
  192. Mo H5
  193. Morris AD189
  194. Moura FA15
  195. Nadler JL190
  196. Nalls MA71, 191, 192
  197. Nayak U61
  198. Ntalla I16
  199. Okada Y3, 19, 20, 21, 193, 194
  200. Orozco L195
  201. Patel SR196
  202. Patil S9
  203. Pei P168
  204. Pereira MA197
  205. Peters A33, 52, 188, 198
  206. Pirie FJ199
  207. Polikowsky HG23
  208. Porneala B166
  209. Prasad G200, 201
  210. Rasmussentorvik LJ67
  211. Reiner AP202
  212. Roden M52, 132, 133
  213. Rohde R31
  214. Roll K27
  215. Sabanayagam C102, 203, 204
  216. Sandow K27
  217. Sankareswaran A62, 184
  218. Sattar N205
  219. Schonherr S157
  220. Shahriar M60
  221. Shen B118
  222. Shi J138
  223. Shin DM30
  224. Shojima N2
  225. Smith JA43, 206
  226. So WY63, 101
  227. Stancakova A158
  228. Steinthorsdottir V45
  229. Stilp AM116
  230. Strauch K207, 208, 209
  231. Taylor KD27
  232. Thorand B33, 52
  233. Thorsteinsdottir U45, 210
  234. Tomlinson B63, 211
  235. Tran TC5
  236. Tsai FJ212
  237. Tuomilehto J213, 214, 215, 216
  238. Tusieluna T217, 218
  239. Udler MS13, 14, 165
  240. Valladaressalgado A219
  241. Van Dam RM42, 175
  242. Van Klinken JB220, 221, 222
  243. Varma R223
  244. Wacherrodarte N224
  245. Wheeler E37
  246. Wickremasinghe AR150
  247. Van Dijk KW220, 221, 225
  248. Witte DR226, 227
  249. Yajnik CS228
  250. Yamamoto K229
  251. Yamamoto K229
  252. Yoon K30
  253. Yu C167, 168
  254. Yuan JM231, 232
  255. Yusuf S34, 35, 89
  256. Zawistowski M9
  257. Zhang L102
  258. Zheng W58
  259. Kanona S16
  260. Van Heel DA286
  261. Raffel LJ233
  262. Igase M234
  263. Ipp E124
  264. Redline S48, 79, 235
  265. Cho YS78
  266. Lind L236
  267. Province MA76
  268. Fornage M237
  269. Hanis CL238
  270. Ingelsson E239, 240
  271. Zonderman AB118
  272. Psaty BM74, 241, 242
  273. Wang YX243
  274. Rotimi CN73
  275. Becker DM72
  276. Matsuda F44
  277. Liu Y90, 244
  278. Yokota M245
  279. Kardia SLR43
  280. Peyser PA43
  281. Pankow JS197
  282. Engert JC246, 247
  283. Bonnefond A98, 99, 248
  284. Froguel P98, 99, 248
  285. Wilson JG249
  286. Sheu WHH140, 142, 250
  287. Wu JY68
  288. Hayes MG251, 252, 253
  289. Ma RCW63, 64, 100, 101
  290. Wong TY102, 203, 204
  291. Mookkanamori DO169
  292. Tuomi T84, 129, 130, 254
  293. Chandak GR62, 255
  294. Collins FS5
  295. Bharadwaj D256
  296. Pare G35, 257
  297. Sale MM61
  298. Ahsan H60
  299. Motala AA199
  300. Shu XO58
  301. Park KS57, 258
  302. Jukema JW55, 259
  303. Cruz M219
  304. Chen YDI27
  305. Rich SS260
  306. Mckeancowdin R54
  307. Grallert H33, 52, 261
  308. Cheng CY102, 203, 204
  309. Ghanbari M121
  310. Tai ES42, 175, 262
  311. Dupuis J174, 263
  312. Kato N32
  313. Laakso M158
  314. Kottgen A50
  315. Koh WP264, 265
  316. Bowden DW112, 266, 267
  317. Palmer CNA268
  318. Kooner JS29, 269, 270, 271
  319. Kooperberg C202
  320. Liu S40, 137, 272
  321. North KE31
  322. Saleheen D273, 274, 275
  323. Hansen T46
  324. Pedersen O46
  325. Wareham NJ37
  326. Lee J30
  327. Kim BJ30
  328. Millwood IY25, 26
  329. Walters RG25, 26
  330. Stefansson K45, 210
  331. Ahlqvist E84
  332. Goodarzi MO83
  333. Mohlke KL69
  334. Langenberg C37, 276, 277
  335. Haiman CA278
  336. Loos RJF22, 46, 279
  337. Florez JC13, 14, 165
  338. Rader DJ12, 280, 281, 282
  339. Ritchie MD12, 283, 284
  340. Zollner S9, 285
  341. Magi R24
  342. Marston NA15
  343. Ruff CT15
  344. Finer S287
  345. Denny JC5, 288
  346. Yamauchi T2
  347. Kadowaki T2, 289
  348. Chambers JC28, 29, 269, 290
  349. Ng MCY112, 267, 291
  350. Sim X42
  351. Below JE23
  352. Tsao PS239, 292, 293
  353. Chang KM10, 294
  354. Mccarthy MI170, 295, 296, 301
  355. Meigs JB13, 165, 166
  356. Mahajan A170, 295, 301
  357. Spracklen CN297
  358. Mercader JM13, 14, 79
  359. Boehnke M9
  360. Rotter JI27
  361. Vujkovic M10, 294, 298
  362. Voight BF10, 11, 12, 281
  363. Morris AP1, 4, 24
  364. Zeggini E4, 299
Show Affiliations
Authors Affiliations
  1. 1. Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, United Kingdom
  2. 2. Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
  3. 3. Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
  4. 4. Institute of Translational Genomics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
  5. 5. Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
  6. 6. British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
  7. 7. Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
  8. 8. Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
  9. 9. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States
  10. 10. Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, United States
  11. 11. Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  12. 12. Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  13. 13. Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, United States
  14. 14. Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
  15. 15. TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
  16. 16. William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
  17. 17. Graduate School of Experimental Medicine, Technical University of Munich, Munich, Germany
  18. 18. Munich School for Data Science, Helmholtz Munich, Neuherberg, Germany
  19. 19. Department of Genome Informatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
  20. 20. Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan
  21. 21. Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  22. 22. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
  23. 23. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
  24. 24. Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
  25. 25. Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
  26. 26. Medical Research Council Population Health Research Unit, University of Oxford, Oxford, United Kingdom
  27. 27. Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States
  28. 28. Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
  29. 29. Department of Cardiology, Ealing Hospital, London NorthWest Healthcare NHS Trust, London, United Kingdom
  30. 30. Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, South Korea
  31. 31. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
  32. 32. Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
  33. 33. Institute of Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
  34. 34. Department of Medicine, McMaster University, Hamilton, ON, Canada
  35. 35. Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada
  36. 36. Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
  37. 37. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
  38. 38. Department of Health Data Science, University of Liverpool, Liverpool, United Kingdom
  39. 39. Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, United States
  40. 40. Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States
  41. 41. Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada
  42. 42. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
  43. 43. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States
  44. 44. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
  45. 45. deCODE Genetics, Amgen, Reykjavik, Iceland
  46. 46. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  47. 47. Department of Biostatistics, Harvard University, Boston, MA, United States
  48. 48. Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, United States
  49. 49. Department of Medicine, Harvard University, Boston, MA, United States
  50. 50. Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
  51. 51. Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston School of Public Health, Houston, TX, United States
  52. 52. German Center for Diabetes Research (DZD), Neuherberg, Germany
  53. 53. Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
  54. 54. Department of Population and Public Health Sciences, Keck School of Medicine of USC, Los Angeles, CA, United States
  55. 55. Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands
  56. 56. Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
  57. 57. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
  58. 58. Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, United States
  59. 59. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
  60. 60. Institute for Population and Precision Health (IPPH), Biological Sciences Division, University of Chicago, Chicago, IL, United States
  61. 61. Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, United States
  62. 62. Genomic Research on Complex Diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India
  63. 63. Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
  64. 64. Chinese University of Hong Kong–Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, Chinese University of Hong Kong, Hong Kong
  65. 65. Samsung Advanced Institute for Health Sciences & amp
  66. 66. Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea
  67. 67. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
  68. 68. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
  69. 69. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
  70. 70. Department of Human Genetics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
  71. 71. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
  72. 72. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
  73. 73. Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
  74. 74. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States
  75. 75. Division of Academics, Ochsner Health, New Orleans, LA, United States
  76. 76. Division of Statistical Genomics, Washington University School of Medicine, St Louis, MO, United States
  77. 77. Department of Research and Evaluation, Division of Biostatistics Research, Kaiser Permanente of Southern California, Pasadena, CA, United States
  78. 78. Department of Biomedical Science, Hallym University, Chuncheon, South Korea
  79. 79. Harvard Medical School, Boston, MA, United States
  80. 80. Metabolic Research Laboratories, Wellcome Trust–Medical Research Council Institute of Metabolic Science, Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
  81. 81. Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
  82. 82. Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran
  83. 83. Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, United States
  84. 84. Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skane University Hospital, Malmo, Sweden
  85. 85. Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
  86. 86. Unidad de Investigacion en Enfermedades Metabolicas and Departamento de Endocrinologia y Metabolismo, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
  87. 87. Steno Diabetes Center Copenhagen, Herlev, Denmark
  88. 88. Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark
  89. 89. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada
  90. 90. Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States
  91. 91. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
  92. 92. Department of Clinical Biochemistry, Vejle Hospital, Vejle, Denmark
  93. 93. Department of Medicine, Division of Endocrinology and Diabetes, Keck School of Medicine of USC, Los Angeles, CA, United States
  94. 94. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
  95. 95. British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, United Kingdom
  96. 96. Health Data Research UK Cambridge, University of Cambridge, Wellcome Genome Campus, Hinxton, United Kingdom
  97. 97. National Institute for Health and Care Research (NIHR) Blood and Transplant Unit (BTRU) in Donor Health and Behaviour, Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
  98. 98. Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille University Hospital, Lille, France
  99. 99. University of Lille, Lille, France
  100. 100. Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong
  101. 101. Hong Kong Institute of Diabetes and Obesity, Chinese University of Hong Kong, Hong Kong
  102. 102. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
  103. 103. Exeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, United Kingdom
  104. 104. Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
  105. 105. Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, United States
  106. 106. Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  107. 107. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
  108. 108. Department of Medicine, University of Vermont, Colchester, VT, United States
  109. 109. Section of Endocrinology and Metabolism, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States
  110. 110. Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
  111. 111. Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece
  112. 112. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, United States
  113. 113. Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
  114. 114. Department of Nephrology and Medical Intensive Care Medicine, Charite–Universitatsmedizin Berlin, Berlin, Germany
  115. 115. Department of Nephrology and Hypertension, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany
  116. 116. Department of Biostatistics, University of Washington, Seattle, WA, United States
  117. 117. California Pacific Medical Center Research Institute, San Francisco, CA, United States
  118. 118. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States
  119. 119. Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia
  120. 120. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom
  121. 121. Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands
  122. 122. Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom
  123. 123. Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States
  124. 124. Department of Medicine, Division of Endocrinology and Metabolism, Lundquist Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States
  125. 125. Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
  126. 126. Centro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Publica, Mexico City, Mexico
  127. 127. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States
  128. 128. Genomics and Computational Biology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  129. 129. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
  130. 130. Folkhalsan Research Center, Helsinki, Finland
  131. 131. University of Exeter Medical School, University of Exeter, Exeter, United Kingdom
  132. 132. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Dusseldorf, Germany
  133. 133. Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Dusseldorf, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
  134. 134. Laboratory for Genomics of Diabetes and Metabolism, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  135. 135. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
  136. 136. Department of Internal Medicine, Diabetes and Metabolism Research Center, Ohio State University Wexner Medical Center, Columbus, OH, United States
  137. 137. Center for Global Cardiometabolic Health, Brown University, Providence, RI, United States
  138. 138. Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
  139. 139. Division of Endocrine and Metabolism, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan
  140. 140. School of Medicine, National Defense Medical Center, Taipei, Taiwan
  141. 141. Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  142. 142. School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  143. 143. Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan
  144. 144. University of Chicago Research Bangladesh, Dhaka, Bangladesh
  145. 145. Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland
  146. 146. Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark
  147. 147. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  148. 148. Faculty of Medicine, Aalborg University, Aalborg, Denmark
  149. 149. Department of Clinical Diabetes, Endocrinology and Metabolism, Department of Translational Research and Cellular Therapeutics, City of Hope, Duarte, CA, United States
  150. 150. Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
  151. 151. Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Osaka, Japan
  152. 152. Department of Geriatric and General Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
  153. 153. Division of General Internal Medicine and Geriatrics, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
  154. 154. Center for Health Information Partnerships, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
  155. 155. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
  156. 156. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea
  157. 157. Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria
  158. 158. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
  159. 159. Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, United States
  160. 160. VA Salt Lake City Health Care System, Salt Lake City, UT, United States
  161. 161. Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
  162. 162. Soochunhyang Institute of Medi-bio Science and Division of Endocrinology, Department of Internal Medicine, Soochunhyang University College of Medicine, Cheonan, South Korea
  163. 163. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  164. 164. USC-Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines
  165. 165. Department of Medicine, Harvard Medical School, Boston, MA, United States
  166. 166. Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, United States
  167. 167. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
  168. 168. Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China
  169. 169. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
  170. 170. Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
  171. 171. Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States
  172. 172. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
  173. 173. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  174. 174. Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States
  175. 175. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
  176. 176. McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, United States
  177. 177. Department of Medicine, Division of Genomics and Bioinformatics, Washington University School of Medicine, St Louis, MO, United States
  178. 178. Department of Biostatistics and Data Science, University of Texas Health Science Center at Houston School of Public Health, Houston, TX, United States
  179. 179. Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmo, Sweden
  180. 180. Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway
  181. 181. Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan
  182. 182. Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Nishihara, Japan
  183. 183. Dromokaiteio Psychiatric Hospital, National and Kapodistrian University of Athens, Athens, Greece
  184. 184. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
  185. 185. Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
  186. 186. Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
  187. 187. Institute of Human Genetics, Technical University Munich, Munich, Germany
  188. 188. German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
  189. 189. Usher Institute to the Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
  190. 190. Department of Medicine and Pharmacology, New York Medical College, Valhalla, NY, United States
  191. 191. Data Tecnica International, Glen Echo, MD, United States
  192. 192. Center for Alzheimer’s and Related Dementias, National Institutes of Health, Bethesda, MD, United States
  193. 193. Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan
  194. 194. Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, Suita, Japan
  195. 195. Instituto Nacional de Medicina Genomica, Mexico City, Mexico
  196. 196. Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
  197. 197. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States
  198. 198. Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-Universitat Munchen, Munich, Germany
  199. 199. Department of Diabetes and Endocrinology, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
  200. 200. Academy of Scientific and Innovative Research, CSIR-Human Resource Development Campus, Ghaziabad, India
  201. 201. Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India
  202. 202. Fred Hutchinson Cancer Research Center, Seattle, WA, United States
  203. 203. Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore
  204. 204. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
  205. 205. School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom
  206. 206. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, United States
  207. 207. Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
  208. 208. Institute for Medical Biostatistics, Epidemiology, and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, Germany
  209. 209. Chair of Genetic Epidemiology, Institute of Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-Universitat Munchen, Munich, Germany
  210. 210. Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  211. 211. Faculty of Medicine, Macau University of Science and Technology, Macao
  212. 212. Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan
  213. 213. Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
  214. 214. National School of Public Health, Madrid, Spain
  215. 215. Department of Public Health, University of Helsinki, Helsinki, Finland
  216. 216. Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
  217. 217. Unidad de Biologia Molecular y Medicina Genomica, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
  218. 218. Departamento de Medicina Genomica y Toxiologia Ambiental, Instituto de Investigaciones Biomedicas, UNAM, Mexico City, Mexico
  219. 219. Unidad de Investigacion Medica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
  220. 220. Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands
  221. 221. Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands
  222. 222. Department of Clinical Chemistry, Laboratory of Genetic Metabolic Disease, Amsterdam University Medical Center, Amsterdam, Netherlands
  223. 223. Southern California Eye Institute, CHA Hollywood Presbyterian Hospital, Los Angeles, CA, United States
  224. 224. Unidad de Investigacion Medica en Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
  225. 225. Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands
  226. 226. Department of Public Health, Aarhus University, Aarhus, Denmark
  227. 227. Danish Diabetes Academy, Odense, Denmark
  228. 228. Diabetology Research Centre, King Edward Memorial Hospital and Research Centre, Pune, India
  229. 229. Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, Japan
  230. 230. Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan
  231. 231. Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States
  232. 232. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States
  233. 233. Department of Pediatrics, Division of Genetic and Genomic Medicine, UCI Irvine School of Medicine, Irvine, CA, United States
  234. 234. Department of Anti-Aging Medicine, Ehime University Graduate School of Medicine, Touon, Japan
  235. 235. Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
  236. 236. Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  237. 237. Institute of Molecular Medicine, University of Texas Health Science Center at Houston School of Public Health, Houston, TX, United States
  238. 238. Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, United States
  239. 239. Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States
  240. 240. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
  241. 241. Department of Epidemiology, University of Washington, Seattle, WA, United States
  242. 242. Department of Health Systems and Population Health, University of Washington, Seattle, WA, United States
  243. 243. Beijing Institute of Ophthalmology, Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, China
  244. 244. Department of Medicine, Division of Cardiology, Duke University School of Medicine, Durham, NC, United States
  245. 245. Kurume University School of Medicine, Kurume, Japan
  246. 246. Department of Medicine, McGill University, Montreal, QC, Canada
  247. 247. Department of Human Genetics, McGill University, Montreal, QC, Canada
  248. 248. Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
  249. 249. Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
  250. 250. Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
  251. 251. Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
  252. 252. Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
  253. 253. Department of Anthropology, Northwestern University, Evanston, IL, United States
  254. 254. Department of Endocrinology, Helsinki University Hospital, Helsinki, Finland
  255. 255. Science and Engineering Research Board (SERB), Department of Science and Technology, Ministry of Science and Technology, Government of India, New Delhi, India
  256. 256. Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
  257. 257. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
  258. 258. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea
  259. 259. Netherlands Heart Institute, Utrecht, Netherlands
  260. 260. Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, United States
  261. 261. Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Munich, Germany
  262. 262. Duke-NUS Medical School, Singapore, Singapore
  263. 263. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada
  264. 264. Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore
  265. 265. Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  266. 266. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, United States
  267. 267. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United States
  268. 268. Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, University of Dundee, Dundee, United Kingdom
  269. 269. Imperial College Healthcare NHS Trust, Imperial College London, London, United Kingdom
  270. 270. MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom
  271. 271. National Heart and Lung Institute, Imperial College London, London, United Kingdom
  272. 272. Department of Medicine, Brown University Alpert School of Medicine, Providence, RI, United States
  273. 273. Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States
  274. 274. Department of Cardiology, Columbia University Irving Medical Center, New York, NY, United States
  275. 275. Center for Non-Communicable Diseases, Karachi, Pakistan
  276. 276. Computational Medicine, Berlin Institute of Health at Charite–Universitatsmedizin, Berlin, Germany
  277. 277. Precision Healthcare University Research Institute, Queen Mary University of London, London, United Kingdom
  278. 278. Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, United States
  279. 279. The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, NY, United States
  280. 280. Division of Translational Medicine and Therapeutics, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  281. 281. Institute for Translational Medicine and Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  282. 282. Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  283. 283. Center for Precision Medicine, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA, United States
  284. 284. Institute for Biomedical Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  285. 285. Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States
  286. 286. Blizard Institute, Queen Mary University of London, London, United Kingdom
  287. 287. Institute for Population Health Sciences, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
  288. 288. All of Us Research Program, National Institutes of Health, Bethesda, MD, United States
  289. 289. Toranomon Hospital, Tokyo, Japan
  290. 290. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
  291. 291. Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
  292. 292. VA Palo Alto Health Care System, Palo Alto, CA, United States
  293. 293. Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
  294. 294. Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  295. 295. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
  296. 296. Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
  297. 297. Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA, United States
  298. 298. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  299. 299. TUM School of Medicine and Health, Technical University of Munich and Klinikum Rechts der Isar, Munich, Germany
  300. 300. Regeneron Genetics Center, Tarrytown, NY, United States
  301. 301. Genentech, South San Francisco, CA, United States

Source: Nature Published:2024


Abstract

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10−8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care. © The Author(s) 2024.
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