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Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways That Link Inflammation and Complex Disorders Publisher Pubmed



Ligthart S1 ; Vaez A2, 3 ; Vosa U4, 5 ; Stathopoulou MG6 ; De Vries PS1, 7 ; Prins BP8 ; Van Der Most PJ2 ; Tanaka T9 ; Naderi E2, 10 ; Rose LM11 ; Wu Y12 ; Karlsson R13 ; Barbalic M14 ; Lin H15 Show All Authors
Authors
  1. Ligthart S1
  2. Vaez A2, 3
  3. Vosa U4, 5
  4. Stathopoulou MG6
  5. De Vries PS1, 7
  6. Prins BP8
  7. Van Der Most PJ2
  8. Tanaka T9
  9. Naderi E2, 10
  10. Rose LM11
  11. Wu Y12
  12. Karlsson R13
  13. Barbalic M14
  14. Lin H15
  15. Pool R16, 17
  16. Zhu G18
  17. Mace A19, 20, 21
  18. Sidore C22
  19. Trompet S23, 24
  20. Mangino M25, 26
  21. Sabaterlleal M27, 28
  22. Kemp JP29, 30
  23. Abbasi A2, 31, 32
  24. Kacprowski T33, 34
  25. Verweij N35
  26. Smith AV36, 37
  27. Huang T38, 39
  28. Marzi C40, 41
  29. Feitosa MF42
  30. Lohman KK43
  31. Kleber ME44
  32. Milaneschi Y45
  33. Mueller C46, 47, 48
  34. Huq M2
  35. Vlachopoulou E49
  36. Lyytikainen LP50, 51
  37. Oldmeadow C52, 53
  38. Deelen J54, 55
  39. Perola M56
  40. Zhao JH57
  41. Feenstra B58
  42. Alizadeh BZ2
  43. Franke L4
  44. Snieder H2
  45. Amini M2
  46. Chasman DI11, 178
  47. Ahluwalia TS97, 98
  48. Tracy RP224
  49. Bis JC220
  50. Eiriksdottir G36
  51. Gross M227
  52. Dupuis J229, 230
  53. Koenig W171, 214, 215
  54. Abbasi A2, 31, 32
  55. Nolte IM2
  56. Daveysmith G30
  57. Morrison AC7
  58. Boerwinkle E225, 226
  59. Morris AP75, 219
  60. Lahti J59, 60, 61
  61. Schraut KE62
  62. Fornage M63
  63. Suktitipat B64
  64. Chen WM65
  65. Li X66
  66. Nutile T67
  67. Malerba G68
  68. Luan J57
  69. Bak T69
  70. Schork N70, 71
  71. Del Greco M F72
  72. Thiering E73, 74
  73. Mahajan A75
  74. Marioni RE76, 77
  75. Mihailov E5
  76. Ozel AB79
  77. Zhang W80, 81
  78. Nethander M82
  79. Cheng YC83
  80. Aslibekyan S84
  81. Ang W85
  82. Gandin I86
  83. Yengo L87, 88
  84. Portas L89
  85. Kooperberg C90
  86. Hofer E91, 92
  87. Rajan KB93
  88. Schurmann C94, 95
  89. Den Hollander W96
  90. Zhao J99
  91. Draisma HHM16, 17, 100
  92. Ford I101
  93. Timpson N30
  94. Teumer A102
  95. Huang H103
  96. Wahl S40, 41
  97. Liu Y43
  98. Huang J104
  99. Uh HW105
  100. Geller F58
  101. Joshi PK62
  102. Yanek LR106
  103. Trabetti E68
  104. Lehne B80
  105. Vozzi D107
  106. Verbanck M87
  107. Biino G108
  108. Saba Y109
  109. Meulenbelt I96
  110. Oconnell JR83
  111. Laakso M110
  112. Giulianini F11
  113. Magnusson PKE13
  114. Ballantyne CM111, 112
  115. Hottenga JJ16
  116. Montgomery GW18
  117. Rivadineira F113
  118. Rueedi R19, 20
  119. Steri M22
  120. Herzig KH114, 115, 116
  121. Stott DJ117
  122. Menni C25
  123. Franberg M28, 118
  124. St Pourcain B30, 119
  125. Felix SB34, 120
  126. Pers TH58, 98
  127. Bakker SJL31
  128. Kraft P103
  129. Peters A121
  130. Vaidya D106
  131. Delgado G44
  132. Smit JH45
  133. Gromann V122
  134. Sinisalo J123
  135. Seppala I50, 51
  136. Williams SR124
  137. Holliday EG52, 53
  138. Moed M54
  139. Langenberg C57
  140. Raikkonen K60
  141. Ding J125
  142. Campbell H62
  143. Sale MM65
  144. Chen YDI66
  145. James AL126, 127
  146. Ruggiero D67, 128
  147. Soranzo N129
  148. Hartman CA69
  149. Smith EN130
  150. Berenson GS131
  151. Fuchsberger C72, 132
  152. Tiesler CMT73, 74
  153. Giedraitis V133
  154. Liewald D76
  155. Fischer K5
  156. Mellstrom D78
  157. Larsson A134
  158. Wang Y135
  159. Scott WR80
  160. Lorentzon M78, 136
  161. Beilby J137, 138
  162. Ryan KA83
  163. Pennell CE85
  164. Vuckovic D139
  165. Balkau B140
  166. Concas MP107
  167. Schmidt R91
  168. Mendes De Leon CF141
  169. Bottinger EP94, 142
  170. Kloppenburg M143, 144
  171. Paternoster L30
  172. Boehnke M145
  173. Musk AW126, 146
  174. Willemsen G16
  175. Evans DM29, 30
  176. Madden PAF147
  177. Kahonen M148, 149
  178. Kutalik Z20, 21
  179. Zoledziewska M22
  180. Karhunen V150
  181. Kritchevsky SB151
  182. Sattar N152
  183. Lachance G25
  184. Clarke R153
  185. Harris TB154
  186. Raitakari OT155, 156
  187. Attia JR52, 53, 157
  188. Van Heemst D24
  189. Kajantie E158, 159, 160
  190. Sorice R67
  191. Gambaro G161
  192. Scott RA57
  193. Hicks AA72
  194. Ferrucci L9
  195. Standl M73
  196. Lindgren CM75, 162, 163
  197. Starr JM76, 164
  198. Karlsson M165
  199. Lind L134
  200. Li JZ79
  201. Chambers JC80, 81, 166, 167, 168
  202. Mori TA85
  203. De Geus EJCN16, 17
  204. Heath AC147
  205. Martin NG18
  206. Auvinen J150, 169
  207. Buckley BM170
  208. De Craen AJM24
  209. Waldenberger M40, 171
  210. Strauch K172, 173
  211. Meitinger T174, 175, 176
  212. Scott RJ52, 177
  213. Mcevoy M52, 53
  214. Beekman M54
  215. Bombieri C68
  216. Ridker PM11, 178
  217. Mohlke KL12
  218. Pedersen NL13
  219. Boomsma DI16
  220. Whitfield JB18
  221. Strachan DP179
  222. Hofman A1
  223. Vollenweider P180
  224. Cucca F22
  225. Jarvelin MR115, 150, 169, 181, 182
  226. Jukema JW23, 183, 184
  227. Spector TD25
  228. Hamsten A28
  229. Zeller T46, 48
  230. Uitterlinden AG1, 113
  231. Nauck M34, 185
  232. Gudnason V36, 37
  233. Qi L39, 186
  234. Grallert H40, 41
  235. Borecki IB187
  236. Rotter JI188
  237. Marz W44, 189, 190
  238. Wild PS48, 122, 191
  239. Lokki ML49
  240. Boyle M157
  241. Salomaa V56
  242. Melbye M58, 192, 193
  243. Eriksson JG56, 61, 78, 194
  244. Wilson JF62, 195
  245. Penninx BWJH45
  246. Becker DM106
  247. Worrall BB196
  248. Gibson G99
  249. Krauss RM197
  250. Ciullo M67, 128
  251. Zaza G198
  252. Wareham NJ57
  253. Oldehinkel AJ69
  254. Palmer LJ199
  255. Murray SS200
  256. Pramstaller PP72, 201, 202
  257. Bandinelli S203
  258. Heinrich J73, 204
  259. Ingelsson E205, 206, 207
  260. Deary IJ76, 208
  261. Magi R5
  262. Vandenput L78
  263. Van Der Harst P35
  264. Desch KC209
  265. Kooner JS81, 166, 168, 210
  266. Ohlsson C78
  267. Hayward C195
  268. Lehtimaki T50, 51
  269. Shuldiner AR83
  270. Arnett DK211
  271. Beilin LJ85
  272. Robino A107
  273. Froguel P87, 212
  274. Pirastu M89
  275. Jess T213
  276. Loos RJF94, 95, 216
  277. Evans DA93
  278. Schmidt H217, 218
  279. Slagboom PE54
  280. Morris AP75, 219
  281. Psaty BM220, 221, 222, 223
  282. Visvikissiest S6
  283. Reiner AP221
  284. Franco OH1, 228
  285. Benjamin EJ15, 229
  286. Dehghan A1, 181
Show Affiliations
Authors Affiliations
  1. 1. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000, CA, Netherlands
  2. 2. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700, RB, Netherlands
  3. 3. Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran
  4. 4. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, 9700, RB, Netherlands
  5. 5. Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 51010, Estonia
  6. 6. Universite de Lorraine, INSERM, IGE-PCV, Nancy, 54000, France
  7. 7. Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, 77030, TX, United States
  8. 8. Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom
  9. 9. Translational Gerontology Branch, National Institute on Aging, Baltimore, 21224, MD, United States
  10. 10. Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, 9713, GZ, Netherlands
  11. 11. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, 02215, MA, United States
  12. 12. Department of Genetics, University of North Carolina, Chapel Hill, 27599, NC, United States
  13. 13. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden
  14. 14. University of Split School of Medicine, Split, 21000, Croatia
  15. 15. Department of Medicine, Boston University School of Medicine, Boston, 02118, MA, United States
  16. 16. Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, 1081, BT, Netherlands
  17. 17. Amsterdam Public Health research institute, VU University Medical Center, Amsterdam, 1081, BT, Netherlands
  18. 18. QIMR Berghofer Medical Research Institute, Brisbane, 4006, QLD, Australia
  19. 19. Department of Computational Biology, University of Lausanne, Lausanne, 1010, Switzerland
  20. 20. Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland
  21. 21. Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, 1010, Switzerland
  22. 22. Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Sardinia, 08045, Italy
  23. 23. Department of Cardiology, Leiden University Medical Center, Leiden 2300 RC, Netherlands
  24. 24. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2333 ZA, Netherlands
  25. 25. Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH, United Kingdom
  26. 26. NIHR Biomedical Research Centre at Guy's and St. Thomas’ Foundation Trust, London, SE1 9RT, United Kingdom
  27. 27. Unit of Genomics of Complex Diseases, Institut d'Investigacio Biomedica Sant Pau, Barcelona, 08025, Spain
  28. 28. Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, 17176, Sweden
  29. 29. University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, 4102, QLD, Australia
  30. 30. MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, United Kingdom
  31. 31. Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, Netherlands
  32. 32. MRC Epidemiology Unit, University of Cambridge School of Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, CB2 0QQ, United Kingdom
  33. 33. Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Greifswald, 17475, Germany
  34. 34. German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald, 17475, Germany
  35. 35. University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, 9713, AV, Netherlands
  36. 36. Icelandic Heart Association, Kopavogur, 201, Iceland
  37. 37. Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland
  38. 38. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, China
  39. 39. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, United States
  40. 40. Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, 85764, Germany
  41. 41. German Center for Diabetes Research, Partner Site Munich, Munich, 85764, Germany
  42. 42. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, 63108-2212, MO, United States
  43. 43. Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, 27157, NC, United States
  44. 44. Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany
  45. 45. Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam University Medical Center/GGZ inGeest Research & Innovation, Amsterdam, 1081, HJ, Netherlands
  46. 46. Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, 20246, Germany
  47. 47. Institute of Medical Biometry and Statistics, University Medical Center Schleswig-Holstein, Campus Luebeck, Lubeck, 23562, Germany
  48. 48. German Center for Cardiovascular Research, Partner Site RhineMain, Mainz, 55131, Germany
  49. 49. Transplantation Laboratory, Medicum, University of Helsinki, Helsinki, 00014, Finland
  50. 50. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33014, Finland
  51. 51. Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33520, Finland
  52. 52. Hunter Medical Research Institute, New Lambon Heights, 2305, NSW, Australia
  53. 53. Centre for Clinical Epidemiology & Biostatistics, Faculty of Health and Medicine, University of Newcastle, Callaghan, 2308, NSW, Australia
  54. 54. Molecular Epidemiology, Leiden University Medical Center, Leiden, 2333, ZC, Netherlands
  55. 55. Max Planck Institute for Biology of Ageing, Cologne, 50931, Germany
  56. 56. National Institute for Health and Welfare, Helsinki, 00271, Finland
  57. 57. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, CB2 0QQ, United Kingdom
  58. 58. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, 2300, Denmark
  59. 59. Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, 00014, Finland
  60. 60. Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland
  61. 61. Folkhalsan Research Centre, Helsinki, 00250, Finland
  62. 62. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH16 4UX, United Kingdom
  63. 63. Human Genetics Center, School of Public Health and Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, 77030, TX, United States
  64. 64. Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand
  65. 65. Center for Public Health Genomics, University of Virginia, Charlottesville, 22908, VA, United States
  66. 66. Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, 90502, CA, United States
  67. 67. Institute of Genetics and Biophysics “A. Buzzati-Traverso, ” Consiglio Nazionale delle Ricerche, Napoli, 80131, Italy
  68. 68. Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, 37134, Italy
  69. 69. Interdisciplinary Center Psychopathology and Emotion regulation, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, Netherlands
  70. 70. Human Biology, J. Craig Venter Institute, La Jolla, 92037, CA, United States
  71. 71. Quantitative Medicine, Translational Genomics Research Institute, Phoenix, 85004, AZ, United States
  72. 72. Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, 39100, Italy
  73. 73. Institute of Epidemiology, Helmholtz Zentrum Munchen – German Research Centre for Environmental Health, Neuherberg, 85764, Germany
  74. 74. Ludwig Maximilian University of Munich, Dr. von Hauner Children's Hospital, Munich, 80337, Germany
  75. 75. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom
  76. 76. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom
  77. 77. Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom
  78. 78. Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg, 41345, Sweden
  79. 79. Department of Human Genetics, University of Michigan, Ann Arbor, 48109-5618, MI, United States
  80. 80. Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, United Kingdom
  81. 81. Department of Cardiology, Ealing Hospital, Middlesex, UB1 3HW, United Kingdom
  82. 82. Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 413 90, Sweden
  83. 83. Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, 21201, MD, United States
  84. 84. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, 35294-0022, AL, United States
  85. 85. Medical School, University of Western Australia, Perth, 6009, WA, Australia
  86. 86. AREA Science Park, Trieste, 34149, Italy
  87. 87. Centre National de la Recherche Scientifique UMR 8199, University of Lille, Institut Pasteur de Lille, European Genomic Institute for Diabetes, FR 3508, Lille, 59000, France
  88. 88. Program in Complex Trait Genomics, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, 4072, QLD, Australia
  89. 89. Support OU, Institute of Genetic and Biomedic Research, Consiglio Nazionale delle Ricerche, Sassari, 7100, Italy
  90. 90. Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Mail Stop M3-A410, 1100 Fairview Ave. N., Seattle, WA, United States
  91. 91. Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Graz, 8036, Austria
  92. 92. Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Graz, 8036, Austria
  93. 93. Department of Internal Medicine, Rush University Medical Center, Chicago, 60612, IL, United States
  94. 94. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, United States
  95. 95. Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, United States
  96. 96. Department of Medical Statistics and Bio-informatics, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, 2333, ZC, Netherlands
  97. 97. Steno Diabetes Center Copenhagen, Gentofte, 2820, Denmark
  98. 98. Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark
  99. 99. Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, 30332, GA, United States
  100. 100. Neuroscience Campus Amsterdam, Amsterdam, 1081, HV, Netherlands
  101. 101. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, G12 8QQ, United Kingdom
  102. 102. Department SHIP-KEF, Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17475, Germany
  103. 103. Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, United States
  104. 104. Boston VA Research Institute, Inc., Boston, 02130, MA, United States
  105. 105. Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden 2333 ZC, Netherlands
  106. 106. GeneSTAR Research Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 21287, MD, United States
  107. 107. Institute for Maternal and Child Health, IRCCS “Burlo Garofolo, ”, Trieste, 34140, Italy
  108. 108. Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche, Pavia, 27100, Italy
  109. 109. Gottfried Schatz Research Center, Institute for Molecular Biology and Biochemistry, Graz, 8010, Austria
  110. 110. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, 70210, Finland
  111. 111. Department of Medicine, Baylor College of Medicine, Houston, 77030, TX, United States
  112. 112. Methodist DeBakey Heart and Vascular Center, Houston, 77030, TX, United States
  113. 113. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 CN, Netherlands
  114. 114. Department of Physiology, Institute of Biomedicine, University of Oulu, Medical Research Center Oulu and Oulu University Hospital, Oulu, 90014, Finland
  115. 115. Biocenter Oulu, University of Oulu, Oulu, 90220, Finland
  116. 116. Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, 60-512, Poland
  117. 117. Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, G12 8QQ, United Kingdom
  118. 118. Department of Numerical Analysis and Computer Science, Stockholm University, Stockholm, 100 44, Sweden
  119. 119. Donders Institute, Radboud University, Nijmegen, 6525, XD, Netherlands
  120. 120. Department for Internal Medicine B, University Medicine Greifswald, Greifswald, 17475, Germany
  121. 121. Institute of Epidemiology II, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherber, 85764, Germany
  122. 122. Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, 55131, Germany
  123. 123. Heart and Lung Center, Helsinki University Hospital and Helsinki University, Helsinki, 00029, Finland
  124. 124. Department of Neurology, University of Virginia, Charlottesville, 22908, VA, United States
  125. 125. Department of Internal Medicine/Geriatrics, Wake Forest University Health Sciences, Winston-Salem, 27157, NC, United States
  126. 126. Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, 6009, WA, Australia
  127. 127. Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, 6009, WA, Australia
  128. 128. IRCCS Neuromed, Pozzilli (IS), 86077, Italy
  129. 129. Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, United Kingdom
  130. 130. Department of Pediatrics and Rady Children's Hospital, School of Medicine, University of California, San Diego, La Jolla, 92037, CA, United States
  131. 131. Center for Cardiovascular Health, Tulane University, New Orleans, 70112, LA, United States
  132. 132. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, 20892, MD, United States
  133. 133. Department of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, Uppsala, 752 37, Sweden
  134. 134. Department of Medical Sciences, Uppsala University, Uppsala, 751 41, Sweden
  135. 135. Department of Medicine, Case Cardiovascular Research Institute, Case Western Reserve University, Harrington Heart & Vascular Institute, University Hospitals, Cleveland, 44106, OH, United States
  136. 136. Geriatric Medicine, Sahlgrenska University Hospital, Molndal, 431 80, Sweden
  137. 137. PathWest Laboratory Medicine WA, Nedlands, 6009, WA, Australia
  138. 138. School of Biomedical Sciences, University of Western Australia, Crawley, Perth, 6009, WA, Australia
  139. 139. Medical Sciences, Surgical and Health Department, University of Trieste, Trieste, 34137, Italy
  140. 140. INSERM U1018, Centre de Recherche en Epidemiologie et Sante des Populations, Team 5 (EpReC, Renal, and Cardiovascular Epidemiology), Universite de Versailles Saint-Quentin-en-Yvelines, Universite Paris-Saclay, Villejuif, 94807, France
  141. 141. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, United States
  142. 142. Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, United States
  143. 143. Department of Rheumatology, Leiden University Medical Center, Leiden, 2300, RC, Netherlands
  144. 144. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333, ZC, Netherlands
  145. 145. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, United States
  146. 146. Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, 6009, WA, Australia
  147. 147. Department of Psychiatry, Washington University School of Medicine, 4560 Clayton Ave., Suite 1000, St. Louis, 63110, MO, United States
  148. 148. Department of Clinical Physiology, Tampere University Hospital, Tampere, 33520, Finland
  149. 149. Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33520, Finland
  150. 150. Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulun yliopisto, 90014, Finland
  151. 151. Gerontology and Geriatric Medicine, Sticht Center on Aging and Rehabilitation, Wake Forest University Health Sciences, Winston-Salem, 27157, NC, United States
  152. 152. BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, G12 8TA, United Kingdom
  153. 153. Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, United Kingdom
  154. 154. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, 20892, MD, United States
  155. 155. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20520, Finland
  156. 156. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland
  157. 157. John Hunter Hospital, New Lambton Heights, 2305, NWS, Australia
  158. 158. Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, 00014, Finland
  159. 159. Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki, 00290, Finland
  160. 160. Department of Obstetrics and Gynaecology, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, 90014, Finland
  161. 161. Division of Nephrology and Dialysis, Columbus-Gemelli University Hospital, Universita Cattolica del Sacro Cuore, Roma, 168, Italy
  162. 162. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, OX3 7FZ, United Kingdom
  163. 163. Program in Medical and Population Genetics, Broad Institute, Cambridge, 02142, MA, United States
  164. 164. Alzheimer's Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom
  165. 165. Department of Clinical Sciences and Orthopaedic Surgery, Lund University, Malmo, 20502, Sweden
  166. 166. Imperial College Healthcare NHS Trust, London, W12 0HS, United Kingdom
  167. 167. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore
  168. 168. MRC-PHE Centre for Environment and Health, Imperial College London, London, W2 1PG, United Kingdom
  169. 169. Unit of Primary Health Care, Oulu University Hospital, Oulu, 90220, Finland
  170. 170. Department of Epidemiology and Public Health, University College Cork, Cork, T12 K8AF, Ireland
  171. 171. German Center for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich, 80636, Germany
  172. 172. Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, 85764, Germany
  173. 173. Genetic Epidemiology, Institute of Medical Informatics, Biometry, and Epidemiology, Faculty of Medicine, Ludwig Maximilian University of Munich, Neuherberg, 85764, Germany
  174. 174. Institute of Human Genetics, Technische Universitat Munchen, Munich, 85764, Germany
  175. 175. Institute of Human Genetics, Helmholtz Zentrum Munchen, Neuherberg, 85764, Germany
  176. 176. Munich Cluster for Systems Neurology (SyNergy), Munich, 81377, Germany
  177. 177. Information-Based Medicine Stream, Hunter Medical Research Institute, New Lambton Heights, 2305, NSW, Australia
  178. 178. Harvard Medical School, Boston, 02115, MA, United States
  179. 179. Population Health Research Institute, St. George's, University of London, London, SW17 0RE, United Kingdom
  180. 180. Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, 1011, Switzerland
  181. 181. Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, W2 1PG, United Kingdom
  182. 182. Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Kingston Lane, Uxbridge, Middlesex, UB8 3PH, United Kingdom
  183. 183. Durrer Center for Cardiogenetic Research, Amsterdam, 3501, DG, Netherlands
  184. 184. Interuniversity Cardiology Institute of the Netherlands, Utrecht, 3511, EP, Netherlands
  185. 185. Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, 17475, Germany
  186. 186. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, 70112, LA, United States
  187. 187. Analytical Genetics Group, Regeneron Genetics Center, Regeneron Pharmaceuticals, Inc., Tarrytown, 10591, NY, United States
  188. 188. Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, 90502, CA, United States
  189. 189. Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, 68161, Germany
  190. 190. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, 8036, Austria
  191. 191. Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, 55131, Germany
  192. 192. Department of Clinical Medicine, University of Copenhagen, Copenhagen, 2300, Denmark
  193. 193. Department of Medicine, Stanford University School of Medicine, Stanford, 94305, CA, United States
  194. 194. Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, 00014, Finland
  195. 195. MRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, United Kingdom
  196. 196. Departments of Neurology and Public Health Sciences, University of Virginia Charlottesville, Charlottesville, 22908-0394, VA, United States
  197. 197. Children's Hospital Oakland Research Institute, Oakland, 94609, CA, United States
  198. 198. Renal Unit, Department of Medicine, Verona University Hospital, Verona, 37126, Italy
  199. 199. School of Public Health, University of Adelaide, Adelaide, 5000, SA, Australia
  200. 200. Department of Pathology, University of California, San Diego, San Diego, 92121, CA, United States
  201. 201. General Central Hospital, Department of Neurology, Bolzano, 39100, Italy
  202. 202. Department of Neurology, University of Lubeck, Lubeck, 23538, Germany
  203. 203. Geriatric Unit, Azienda Sanitaria Firenze, Florence, 50122, Italy
  204. 204. Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich, Member DZL, German Center for Lung Research, Munich, 81377, Germany
  205. 205. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 751 41, Sweden
  206. 206. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, 94305, CA, United States
  207. 207. Stanford Cardiovascular Institute, Stanford University, Stanford, 94305, CA, United States
  208. 208. Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom
  209. 209. Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, 48109, MI, United States
  210. 210. National Heart and Lung Institute, Imperial College London, London, W12 0NN, United Kingdom
  211. 211. University of Kentucky, College of Public Health, Lexington, 40508, KY, United States
  212. 212. Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, SW7 2AZ, United Kingdom
  213. 213. Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, 2200, Denmark
  214. 214. Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, 80801, Germany
  215. 215. Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Munich, 80636, Germany
  216. 216. Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, 10029-6542, NY, United States
  217. 217. Department of Neurology, Medical University Graz, Graz, 8010, Austria
  218. 218. Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, 8010, Austria
  219. 219. Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, United Kingdom
  220. 220. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, 98101, WA, United States
  221. 221. Department of Epidemiology, University of Washington, Seattle, 98101, WA, United States
  222. 222. Department of Health Services, University of Washington, Seattle, 98195-7660, WA, United States
  223. 223. Kaiser Permanente Washington Health Research Institute, Seattle, 98101, WA, United States
  224. 224. Department of Pathology, University of Vermont, Colchester, 05405, VT, United States
  225. 225. Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, 77030, TX, United States
  226. 226. Human Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, TX, United States
  227. 227. Department of Lab Medicine and Pathology, University of Minnesota, Minneapolis, 55455, MN, United States
  228. 228. Institute of Social and Preventive Medicine, University of Bern, Bern, 3012, Switzerland
  229. 229. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, 01702, MA, United States
  230. 230. Department of Biostatistics, Boston University School of Public Health, Boston, 02118, MA, United States

Source: American Journal of Human Genetics Published:2018


Abstract

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10−8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences. © 2018 American Society of Human Genetics
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