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Nat Genet. 2019 Jun;51(6):957-972. doi: 10.1038/s41588-019-0407-x. Epub 2019 May 31.

A catalog of genetic loci associated with kidney function from analyses of a million individuals.

Wuttke M1,2, Li Y1, Li M3, Sieber KB4, Feitosa MF5, Gorski M6,7, Tin A8,9, Wang L5, Chu AY10, Hoppmann A1, Kirsten H11,12, Giri A13,14, Chai JF15, Sveinbjornsson G16, Tayo BO17, Nutile T18, Fuchsberger C19, Marten J20, Cocca M21, Ghasemi S22,23, Xu Y3, Horn K11,12, Noce D19, van der Most PJ24, Sedaghat S25, Yu Z8,26, Akiyama M27,28, Afaq S29,30, Ahluwalia TS31, Almgren P32, Amin N25, Ärnlöv J33,34, Bakker SJL35, Bansal N36,37, Baptista D38, Bergmann S39,40,41, Biggs ML42,43, Biino G44, Boehnke M45, Boerwinkle E46, Boissel M47, Bottinger EP48,49, Boutin TS20, Brenner H50,51, Brumat M52, Burkhardt R12,53,54, Butterworth AS55,56, Campana E52, Campbell A57, Campbell H58, Canouil M47, Carroll RJ59, Catamo E21, Chambers JC29,60,61,62,63, Chee ML64, Chee ML64, Chen X65, Cheng CY64,66,67, Cheng Y1, Christensen K68, Cifkova R69,70, Ciullo M18,71, Concas MP21, Cook JP72, Coresh J8, Corre T39,40,73, Sala CF74, Cusi D75,76, Danesh J77, Daw EW5, de Borst MH35, De Grandi A19, de Mutsert R78, de Vries APJ79, Degenhardt F80, Delgado G81, Demirkan A25, Di Angelantonio E82,83, Dittrich K84,85, Divers J86, Dorajoo R87, Eckardt KU88,89, Ehret G38, Elliott P90,91,92,93, Endlich K23,94, Evans MK95, Felix JF25,96,97, Foo VHX64, Franco OH25,98, Franke A80, Freedman BI99, Freitag-Wolf S100, Friedlander Y101, Froguel P47,102, Gansevoort RT35, Gao H90, Gasparini P21,52, Gaziano JM103, Giedraitis V104, Gieger C105,106,107, Girotto G21,52, Giulianini F108, Gögele M19, Gordon SD109, Gudbjartsson DF16, Gudnason V110,111, Haller T112, Hamet P113,114, Harris TB115, Hartman CA116, Hayward C20, Hellwege JN117,118,119, Heng CK120,121, Hicks AA19, Hofer E122,123, Huang W124,125, Hutri-Kähönen N126,127, Hwang SJ128,129, Ikram MA25, Indridason OS130, Ingelsson E131,132,133,134, Ising M135, Jaddoe VWV25,96,97, Jakobsdottir J136, Jonas JB137,138, Joshi PK58, Josyula NS139, Jung B6, Kähönen M140,141, Kamatani Y27,142, Kammerer CM143, Kanai M27,144, Kastarinen M145, Kerr SM20, Khor CC64,87, Kiess W12,84,85, Kleber ME81, Koenig W146,147,148, Kooner JS61,62,63,149, Körner A12,84,85, Kovacs P150, Kraja AT5, Krajcoviechova A69,70, Kramer H17,151, Krämer BK81, Kronenberg F152, Kubo M153, Kühnel B105, Kuokkanen M154,155, Kuusisto J145,156, La Bianca M21, Laakso M145,156, Lange LA157, Langefeld CD86, Lee JJ15, Lehne B29, Lehtimäki T158,159, Lieb W160; Lifelines Cohort Study, Lim SC15,161, Lind L162, Lindgren CM163,164, Liu J25, Liu J87,165, Loeffler M11,12, Loos RJF48,166, Lucae S135, Lukas MA167, Lyytikäinen LP158,159, Mägi R112, Magnusson PKE65, Mahajan A168,169, Martin NG109, Martins J170, März W171,172,173, Mascalzoni D19, Matsuda K174, Meisinger C175,176, Meitinger T147,177,178, Melander O179, Metspalu A112, Mikaelsdottir EK16, Milaneschi Y180, Miliku K25,96,97, Mishra PP158,159; V. A. Million Veteran Program, Mohlke KL181, Mononen N158,159, Montgomery GW182, Mook-Kanamori DO78,183, Mychaleckyj JC184, Nadkarni GN48,185, Nalls MA186,187, Nauck M23,188, Nikus K189,190, Ning B191, Nolte IM24, Noordam R192, O'Connell J193, O'Donoghue ML194,195, Olafsson I196, Oldehinkel AJ116, Orho-Melander M32, Ouwehand WH77, Padmanabhan S197, Palmer ND198, Palsson R111,130, Penninx BWJH180, Perls T199, Perola M200, Pirastu M201, Pirastu N58, Pistis G202, Podgornaia AI10, Polasek O203,204, Ponte B205, Porteous DJ57,206, Poulain T12, Pramstaller PP19, Preuss MH48, Prins BP55, Province MA5, Rabelink TJ79,207, Raffield LM181, Raitakari OT208,209, Reilly DF10, Rettig R210, Rheinberger M6, Rice KM43, Ridker PM108,211, Rivadeneira F25,212, Rizzi F213,214, Roberts DJ215, Robino A21, Rossing P31, Rudan I58, Rueedi R39,40, Ruggiero D18,71, Ryan KA216, Saba Y217, Sabanayagam C64, Salomaa V200, Salvi E213,218, Saum KU50, Schmidt H219, Schmidt R122, Schöttker B50,51, Schulz CA32, Schupf N220,221,222, Shaffer CM59, Shi Y64, Smith AV111, Smith BH223, Soranzo N224, Spracklen CN181, Strauch K225,226, Stringham HM45, Stumvoll M227, Svensson PO228,229, Szymczak S100, Tai ES15,165,230, Tajuddin SM95, Tan NYQ64, Taylor KD231, Teren A12,232, Tham YC64, Thiery J12,53, Thio CHL24, Thomsen H233, Thorleifsson G16, Toniolo D74, Tönjes A227, Tremblay J113,234, Tzoulaki I90,235, Uitterlinden AG212, Vaccargiu S201, van Dam RM15,165, van der Harst P236,237,238, van Duijn CM25, Velez Edward DR119,239, Verweij N236, Vogelezang S25,96,97, Völker U23,240, Vollenweider P241, Waeber G241, Waldenberger M105,106,147, Wallentin L242,243, Wang YX138, Wang C87,244, Waterworth DM4, Bin Wei W245, White H246, Whitfield JB109, Wild SH247, Wilson JF20,58, Wojczynski MK5, Wong C67, Wong TY64,67, Xu L138, Yang Q191, Yasuda M64,248, Yerges-Armstrong LM4, Zhang W61,90, Zonderman AB95, Rotter JI231,249,250, Bochud M73, Psaty BM251,252, Vitart V20, Wilson JG253, Dehghan A29,90, Parsa A254,255, Chasman DI108,211, Ho K256,257, Morris AP72,168, Devuyst O258, Akilesh S37,259, Pendergrass SA260, Sim X15, Böger CA6,261, Okada Y262,263, Edwards TL119,118, Snieder H24, Stefansson K16, Hung AM119,264, Heid IM7, Scholz M11,12, Teumer A22,23, Köttgen A265,266, Pattaro C267.

Author information

1
Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
2
Renal Division, Department of Medicine IV, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
3
Division of Nephrology and Hypertension, Department of Medicine, University of Utah, Salt Lake City, USA.
4
Target Sciences-Genetics, GlaxoSmithKline, Collegeville, PA, USA.
5
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
6
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
7
Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
8
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
9
Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, MD, USA.
10
Genetics, Merck & Co., Inc, Kenilworth, NJ, USA.
11
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
12
LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
13
Division of Quantitative Sciences, Department of Obstetrics & Gynecology, Vanderbilt Genetics Institute, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, USA.
14
Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, USA.
15
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
16
deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
17
Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, USA.
18
Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso'-CNR, Naples, Italy.
19
Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.
20
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
21
Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
22
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
23
DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
24
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
25
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
26
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
27
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
28
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
29
Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
30
Institute of Public Health & Social Sciences, Khyber Medical University, Peshawar, Pakistan.
31
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
32
Diabetes and Cardiovascular Disease-Genetic Epidemiology, Department of Clincial Sciences in Malmö, Lund University, Malmö, Sweden.
33
Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
34
School of Health and Social Studies, Dalarna University, Stockholm, Sweden.
35
Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
36
Division of Nephrology, University of Washington, Seattle, WA, USA.
37
Kidney Research Institute, University of Washington, Seattle, WA, USA.
38
Cardiology, Geneva University Hospitals, Geneva, Switzerland.
39
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
40
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
41
Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
42
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
43
Department of Biostatistics, University of Washington, Seattle, WA, USA.
44
Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy.
45
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
46
Human Genetics Center, University of Texas Health Science Center, Houston, TX, USA.
47
CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
48
Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
49
Digital Health Center, Hasso Plattner Institute and University of Potsdam, Potsdam, Germany.
50
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
51
Network Aging Research, University of Heidelberg, Heidelberg, Germany.
52
Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
53
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany.
54
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
55
MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
56
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
57
Center for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
58
Center for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
59
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
60
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
61
Department of Cardiology, Ealing Hospital, Middlesex, UK.
62
Imperial College Healthcare NHS Trust, Imperial College London, London, UK.
63
MRC-PHE Center for Environment and Health, School of Public Health, Imperial College London, London, UK.
64
Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.
65
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
66
Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
67
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
68
Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, Southern Denmark University, Odense, Denmark.
69
Center for Cardiovascular Prevention, Charles University in Prague, First Faculty of Medicine and Thomayer Hospital, Prague, Czech Republic.
70
Department of Medicine II, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic.
71
IRCCS Neuromed, Pozzilli, Italy.
72
Department of Biostatistics, University of Liverpool, Liverpool, UK.
73
Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
74
San Raffaele Research Institute, Milan, Italy.
75
Institute of Biomedical Technologies, National Research Council of Italy, Milan, Italy.
76
Bio4Dreams-Business Nursery for Life Sciences, Milan, Italy.
77
Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
78
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
79
Section of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
80
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
81
Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
82
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
83
NHS Blood and Transplant, Cambridge, UK.
84
Department of Women and Child Health, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
85
Center for Pediatric Research, University of Leipzig, Leipzig, Germany.
86
Public Health Sciences-Biostatistics, Wake Forest School of Medicine, Winston-Salem, NC, USA.
87
Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.
88
Intensive Care Medicine, Charité, Berlin, Germany.
89
Department of Nephrology and Hypertension, Friedrich Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
90
Department of Epidemiology and Biostatistics, MRC-PHE Center for Environment and Health, School of Public Health, Imperial College London, London, UK.
91
Imperial College NIHR Biomedical Research Center, Imperial College London, London, UK.
92
Dementia Research Institute, Imperial College London, London, UK.
93
Health Data Research UK-London, London, UK.
94
Department of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany.
95
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, US National Institutes of Health, Baltimore, MD, USA.
96
Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
97
Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
98
Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
99
Section on Nephrology, Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
100
Institute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein, Kiel, Germany.
101
School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
102
Department of Genomics of Common Disease, Imperial College London, London, UK.
103
Massachusetts Veterans Epidemiology Research and Information Center, VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, USA.
104
Molecular Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
105
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
106
Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
107
German Center for Diabetes Research (DZD), Neuherberg, Germany.
108
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
109
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
110
Icelandic Heart Association, Kopavogur, Iceland.
111
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
112
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
113
Montreal University Hospital Research Center, CHUM, Montreal, Quebec, Canada.
114
Medpharmgene, Montreal, Quebec, Canada.
115
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, US National Institutes of Health, Bethesda, MD, USA.
116
Interdisciplinary Center of Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
117
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
118
Division of Epidemiology, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
119
Department of Veteran's Affairs, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, USA.
120
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
121
Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore.
122
Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
123
Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
124
Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai, China.
125
Shanghai Industrial Technology Institute, Shanghai, China.
126
Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
127
Department of Pediatrics, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
128
NHLBI's Framingham Heart Study, Framingham, MA, USA.
129
The Center for Population Studies, NHLBI, Framingham, MA, USA.
130
Division of Nephrology, Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
131
Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
132
Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
133
Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
134
Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA.
135
Max Planck Institute of Psychiatry, Munich, Germany.
136
The Center of Public Health Sciences, University of Iceland, Reykjavík, Iceland.
137
Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.
138
Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
139
Geisinger Research, Biomedical and Translational Informatics Institute, Rockville, MD, USA.
140
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
141
Department of Clinical Physiology, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
142
Kyoto-McGill International Collaborative School in Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
143
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
144
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
145
Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
146
Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
147
DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
148
Institute of Epidemiology and Biostatistics, University of Ulm, Ulm, Germany.
149
National Heart and Lung Institute, Imperial College London, London, UK.
150
Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Leipzig, Germany.
151
Division of Nephrology and Hypertension, Loyola University Chicago, Chicago, IL, USA.
152
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
153
RIKEN Center for Integrative Medical Sciences (IMS), Yokohama (Kanagawa), Japan.
154
The Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
155
Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland.
156
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
157
Division of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado Denver-Anschutz Medical Campus, Aurora, CO, USA.
158
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
159
Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
160
Institute of Epidemiology and Biobank Popgen, Kiel University, Kiel, Germany.
161
Diabetes Center, Khoo Teck Puat Hospital, Singapore, Singapore.
162
Cardiovascular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
163
Nuffield Department of Medicine, University of Oxford, Oxford, UK.
164
Broad Institute of Harvard and MIT, Cambridge, MA, USA.
165
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
166
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
167
Target Sciences-Genetics, GlaxoSmithKline, Albuquerque, NM, USA.
168
Wellcome Trust Center for Human Genetics, University of Oxford, Oxford, UK.
169
Oxford Center for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
170
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
171
Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany.
172
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
173
Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
174
Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
175
Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
176
Chair of Epidemiology, Ludwig- Maximilians-Universität München at UNIKA-T Augsburg, Augsburg, Germany.
177
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
178
Institute of Human Genetics, Technische Universität München, Munich, Germany.
179
Hypertension and Cardiovascular Disease, Department of Clincial Sciences Malmö, Lund University, Malmö, Sweden.
180
Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
181
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
182
Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.
183
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
184
Center for Public Health Genomics, University of Virginia, Charlottesville, Charlottesville, VA, USA.
185
Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
186
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
187
Data Tecnica International, Glen Echo, MD, USA.
188
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
189
Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, Finland.
190
Department of Cardiology, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland.
191
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
192
Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
193
University of Maryland School of Medicine, Baltimore, MD, USA.
194
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
195
TIMI Study Group, Boston, MA, USA.
196
Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.
197
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
198
Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
199
Department of Medicine, Geriatrics Section, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
200
National Institute for Health and Welfare, Helsinki, Finland.
201
Institute of Genetic and Biomedical Research, National Research Council of Italy, UOS of Sassari, Li Punti, Sassari, Italy.
202
Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
203
Faculty of Medicine, University of Split, Split, Croatia.
204
Gen-info Ltd, Zagreb, Croatia.
205
Service de Néphrologie, Geneva University Hospitals, Geneva, Switzerland.
206
Center for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
207
Einthoven Laboratory of Experimental Vascular Research, Leiden University Medical Center, Leiden, the Netherlands.
208
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
209
Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
210
Institute of Physiology, University Medicine Greifswald, Karlsburg, Germany.
211
Harvard Medical School, Boston, MA, USA.
212
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
213
Department of Health Sciences, University of Milan, Milano, Italy.
214
ePhood Scientific Unit, ePhood SRL, Milano, Italy.
215
NHS Blood and Transplant, BRC Oxford Haematology Theme; Nuffield Division of Clinical Laboratory Sciences; University of Oxford, Oxford, UK.
216
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.
217
Molecular Biology and Biochemistry, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria.
218
Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy.
219
Institute of Molecular Biology and Biochemistry, Center for Molecular Medicine, Medical University of Graz, Graz, Austria.
220
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
221
Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA.
222
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, USA.
223
Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
224
Human Genetics, Wellcome Sanger Institute, Hinxton, UK.
225
Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
226
Chair of Genetic Epidemiology, IBE, Faculty of Medicine, Ludwig-Maximilians-Universität München, München, Germany.
227
Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
228
Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
229
Department of Cardiology, Södersjukhuset, Stockholm, Sweden.
230
Duke-NUS Medical School, Singapore, Singapore.
231
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
232
Heart Center Leipzig, Leipzig, Germany.
233
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
234
CRCHUM, Montreal, Canada.
235
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
236
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
237
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
238
Durrer Center for Cardiovascular Research, The Netherlands Heart Institute, Utrecht, the Netherlands.
239
Department of Obstetrics and Gynecology, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, USA.
240
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
241
Internal Medicine, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
242
Cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
243
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
244
School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
245
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
246
Green Lane Cardiovascular Service, Auckland City Hospital and University of Auckland, Auckland, New Zealand.
247
Center for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
248
Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
249
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
250
Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
251
Cardiovascular Health Research Unit, Department of Medicine, Department of Epidemiology, Department of Health Service, University of Washington, Seattle, WA, USA.
252
Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
253
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
254
Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
255
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
256
Kidney Health Research Institute (KHRI), Geisinger, Danville, PA, USA.
257
Department of Nephrology, Geisinger, Danville, PA, USA.
258
Institute of Physiology, University of Zurich, Zurich, Switzerland.
259
Anatomic Pathology, University of Washington Medical Center, Seattle, WA, USA.
260
Geisinger Research, Biomedical and Translational Informatics Institute, Danville, PA, USA.
261
Department of Nephrology and Rheumatology, Kliniken Südostbayern, Regensburg, Germany.
262
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences (IMS), Osaka, Japan.
263
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
264
Vanderbilt University Medical Center, Division of Nephrology & Hypertension, Nashville, TN, USA.
265
Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany. anna.koettgen@uniklinik-freiburg.de.
266
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. anna.koettgen@uniklinik-freiburg.de.
267
Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy. cristian.pattaro@eurac.edu.

Abstract

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

PMID:
31152163
DOI:
10.1038/s41588-019-0407-x
[Indexed for MEDLINE]

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