Abstract

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

Details

Title
Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
Author
Teumer, Alexander 1   VIAFID ORCID Logo  ; Li, Yong 2   VIAFID ORCID Logo  ; Ghasemi, Sahar 1 ; Prins, Bram P 3 ; Wuttke, Matthias 4   VIAFID ORCID Logo  ; Hermle, Tobias 5 ; Giri, Ayush 6   VIAFID ORCID Logo  ; Sieber, Karsten B 7 ; Qiu, Chengxiang 8   VIAFID ORCID Logo  ; Kirsten, Holger 9   VIAFID ORCID Logo  ; Tin, Adrienne 10   VIAFID ORCID Logo  ; Chu, Audrey Y 11 ; Bansal, Nisha 12 ; Feitosa, Mary F 13   VIAFID ORCID Logo  ; Wang, Lihua 13 ; Jin-Fang, Chai 14   VIAFID ORCID Logo  ; Cocca, Massimiliano 15   VIAFID ORCID Logo  ; Fuchsberger, Christian 16 ; Gorski, Mathias 17   VIAFID ORCID Logo  ; Hoppmann, Anselm 2 ; Horn, Katrin 9   VIAFID ORCID Logo  ; Li, Man 18   VIAFID ORCID Logo  ; Marten, Jonathan 19   VIAFID ORCID Logo  ; Noce, Damia 16 ; Nutile, Teresa 20 ; Sedaghat, Sanaz 21 ; Sveinbjornsson, Gardar 22 ; Tayo, Bamidele O 23 ; Peter J van der Most 24   VIAFID ORCID Logo  ; Xu, Yizhe 18 ; Yu, Zhi 25 ; Gerstner, Lea 5 ; Ärnlöv, Johan 26 ; Bakker, Stephan J L 27 ; Baptista, Daniela 28 ; Biggs, Mary L 29 ; Boerwinkle, Eric 30 ; Brenner, Hermann 31 ; Burkhardt, Ralph 32   VIAFID ORCID Logo  ; Carroll, Robert J 33 ; Miao-Li, Chee 34 ; Miao-Ling, Chee 34 ; Chen, Mengmeng 5 ; Ching-Yu, Cheng 35 ; Cook, James P 36 ; Coresh, Josef 37   VIAFID ORCID Logo  ; Corre, Tanguy 38 ; Danesh, John 39 ; de Borst, Martin H 27   VIAFID ORCID Logo  ; De Grandi, Alessandro 16 ; de Mutsert, Renée 40 ; Aiko P J de Vries 41 ; Degenhardt, Frauke 42 ; Dittrich, Katalin 43 ; Divers, Jasmin 44 ; Eckardt, Kai-Uwe 45 ; Ehret, Georg 28   VIAFID ORCID Logo  ; Endlich, Karlhans 46   VIAFID ORCID Logo  ; Felix, Janine F 47   VIAFID ORCID Logo  ; Franco, Oscar H 48 ; Franke, Andre 42   VIAFID ORCID Logo  ; Freedman, Barry I 49   VIAFID ORCID Logo  ; Freitag-Wolf, Sandra 50   VIAFID ORCID Logo  ; Gansevoort, Ron T 27 ; Giedraitis, Vilmantas 51   VIAFID ORCID Logo  ; Gögele, Martin 16 ; Grundner-Culemann, Franziska 2   VIAFID ORCID Logo  ; Gudbjartsson, Daniel F 22 ; Gudnason, Vilmundur 52   VIAFID ORCID Logo  ; Hamet, Pavel 53 ; Harris, Tamara B 54 ; Hicks, Andrew A 16   VIAFID ORCID Logo  ; Holm, Hilma 22 ; Valencia Hui Xian Foo 34 ; Shih-Jen Hwang 55 ; Ikram, M Arfan 21   VIAFID ORCID Logo  ; Ingelsson, Erik 56   VIAFID ORCID Logo  ; Jaddoe, Vincent W V 47   VIAFID ORCID Logo  ; Jakobsdottir, Johanna 57 ; Navya, Shilpa Josyula 58   VIAFID ORCID Logo  ; Jung, Bettina 59 ; Kähönen, Mika 60 ; Khor, Chiea-Chuen 61   VIAFID ORCID Logo  ; Kiess, Wieland 62 ; Koenig, Wolfgang 63   VIAFID ORCID Logo  ; Körner, Antje 62 ; Kovacs, Peter 64   VIAFID ORCID Logo  ; Kramer, Holly 65 ; Krämer, Bernhard K 66 ; Kronenberg, Florian 67   VIAFID ORCID Logo  ; Lange, Leslie A 68 ; Langefeld, Carl D 44 ; Jeannette Jen-Mai Lee 14 ; Lehtimäki, Terho 69 ; Lieb, Wolfgang 70 ; Su-Chi, Lim 71 ; Lind, Lars 72 ; Lindgren, Cecilia M 73   VIAFID ORCID Logo  ; Liu, Jianjun 74   VIAFID ORCID Logo  ; Loeffler, Markus 9 ; Leo-Pekka Lyytikäinen 69   VIAFID ORCID Logo  ; Mahajan, Anubha 75   VIAFID ORCID Logo  ; Maranville, Joseph C 76 ; Mascalzoni, Deborah 16   VIAFID ORCID Logo  ; McMullen, Barbara 77 ; Meisinger, Christa 78 ; Meitinger, Thomas 79 ; Miliku, Kozeta 47   VIAFID ORCID Logo  ; Mook-Kanamori, Dennis O 80 ; Müller-Nurasyid, Martina 81   VIAFID ORCID Logo  ; Mychaleckyj, Josyf C 82   VIAFID ORCID Logo  ; Nauck, Matthias 83 ; Nikus, Kjell 84 ; Boting Ning 85 ; Noordam, Raymond 86 ; Jeffrey O’ Connell 87 ; Olafsson, Isleifur 88 ; Palmer, Nicholette D 89   VIAFID ORCID Logo  ; Peters, Annette 90 ; Podgornaia, Anna I 11 ; Ponte, Belen 91 ; Poulain, Tanja 92   VIAFID ORCID Logo  ; Pramstaller, Peter P 16 ; Rabelink, Ton J 93 ; Raffield, Laura M 94   VIAFID ORCID Logo  ; Reilly, Dermot F 11 ; Rettig, Rainer 95 ; Rheinberger, Myriam 59 ; Rice, Kenneth M 96   VIAFID ORCID Logo  ; Rivadeneira, Fernando 97   VIAFID ORCID Logo  ; Runz, Heiko 98 ; Ryan, Kathleen A 99 ; Charumathi Sabanayagam 100   VIAFID ORCID Logo  ; Saum, Kai-Uwe 101 ; Schöttker, Ben 31 ; Shaffer, Christian M 33 ; Shi, Yuan 100 ; Smith, Albert V 102   VIAFID ORCID Logo  ; Strauch, Konstantin 103 ; Stumvoll, Michael 104 ; Sun, Benjamin B 3   VIAFID ORCID Logo  ; Szymczak, Silke 50   VIAFID ORCID Logo  ; E-Shyong, Tai 105 ; Tan, Nicholas Y Q 34 ; Taylor, Kent D 106   VIAFID ORCID Logo  ; Teren, Andrej 107 ; Yih-Chung Tham 34 ; Thiery, Joachim 108 ; Thio, Chris H L 24   VIAFID ORCID Logo  ; Thomsen, Hauke 109 ; Thorsteinsdottir, Unnur 22 ; Tönjes, Anke 104 ; Tremblay, Johanne 110 ; Uitterlinden, André G 111   VIAFID ORCID Logo  ; Pim van der Harst 112   VIAFID ORCID Logo  ; Verweij, Niek 113   VIAFID ORCID Logo  ; Vogelezang, Suzanne 47 ; Völker, Uwe 114   VIAFID ORCID Logo  ; Waldenberger, Melanie 115 ; Wang, Chaolong 116   VIAFID ORCID Logo  ; Wilson, Otis D 117 ; Wong, Charlene 118 ; Tien-Yin, Wong 35 ; Yang, Qiong 85   VIAFID ORCID Logo  ; Yasuda, Masayuki 119 ; Akilesh, Shreeram 120 ; Bochud, Murielle 121 ; Böger, Carsten A 122 ; Devuyst, Olivier 123   VIAFID ORCID Logo  ; Edwards, Todd L 124   VIAFID ORCID Logo  ; Ho, Kevin 125   VIAFID ORCID Logo  ; Morris, Andrew P 126   VIAFID ORCID Logo  ; Parsa, Afshin 127 ; Pendergrass, Sarah A 128   VIAFID ORCID Logo  ; Psaty, Bruce M 129 ; Rotter, Jerome I 130   VIAFID ORCID Logo  ; Stefansson, Kari 22   VIAFID ORCID Logo  ; Wilson, James G 131 ; Susztak, Katalin 8   VIAFID ORCID Logo  ; Snieder, Harold 24 ; Heid, Iris M 132 ; Scholz, Markus 9   VIAFID ORCID Logo  ; Butterworth, Adam S 133   VIAFID ORCID Logo  ; Hung, Adriana M 134   VIAFID ORCID Logo  ; Pattaro, Cristian 16   VIAFID ORCID Logo  ; Köttgen, Anna 135   VIAFID ORCID Logo 

 Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany 
 Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany 
 MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK 
 Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany; Renal Division, Department of Medicine, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany 
 Renal Division, Department of Medicine, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany 
 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; Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, USA 
 Target Sciences - Genetics, GlaxoSmithKline, Collegeville, PA, USA 
 Renal Electrolyte and Hypertension Division, Department of Medicine, Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, USA 
 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; LIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany 
10  Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Epidemiology and Clinical Research, Welch Centre for Prevention, Baltimore, MD, USA 
11  Genetics, Merck & Co., Inc., Kenilworth, NJ, USA 
12  Division of Nephrology, University of Washington, Seattle, WA, USA; Kidney Research Institute, University of Washington, Seattle, WA, USA 
13  Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA 
14  Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore 
15  Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, Trieste, Italy 
16  Eurac Research, Institute for Biomedicine (affiliated to the University of Lübeck), Bolzano, Italy 
17  Department of Nephrology, University Hospital Regensburg, Regensburg, Germany; Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany 
18  Department of Medicine, Division of Nephrology and Hypertension, University of Utah, Salt Lake City, UT, USA 
19  Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK 
20  Institute of Genetics and Biophysics “Adriano Buzzati-Traverso” - CNR, Naples, Italy 
21  Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands 
22  deCODE Genetics, Amgen Inc., Reykjavik, Iceland 
23  Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, USA 
24  Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 
25  Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA 
26  Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden 
27  Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 
28  Cardiology, Geneva University Hospitals, Geneva, Switzerland 
29  Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Department of Biostatistics, University of Washington, Seattle, WA, USA 
30  Human Genetics Centre, University of Texas Health Science Centre, Houston, TX, USA 
31  Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg, Germany; Network Aging Research, University of Heidelberg, Heidelberg, Germany 
32  LIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany; Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany 
33  Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA 
34  Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore 
35  Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore 
36  Department of Biostatistics, University of Liverpool, Liverpool, UK 
37  Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA 
38  Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland 
39  Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK 
40  Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands 
41  Section of Nephrology, Department of Internal Medicine, Leiden University Medical Centre, Leiden, The Netherlands 
42  Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany 
43  Department of Women and Child Health, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany; Centre for Pediatric Research, University of Leipzig, Leipzig, Germany 
44  Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA 
45  Intensive Care Medicine, Charité, Berlin, Germany; Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany 
46  DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany; Department of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany 
47  Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands 
48  Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland 
49  Internal Medicine - Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA 
50  Institute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein, Kiel, USA 
51  Department of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, Uppsala, Sweden 
52  Icelandic Heart Association, Kopavogur, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland 
53  Montreal University Hospital Research Centre, CHUM, Montreal, QC, Canada; Medpharmgene, Montreal, QC, Canada 
54  Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA 
55  NHLBI’s Framingham Heart Study, Framingham, MA, USA; The Centre for Population Studies, NHLBI, Framingham, MA, USA 
56  Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA 
57  Icelandic Heart Association, Holtasmari 1, Kopavogur, Iceland; The Centre of Public Health Sciences, University of Iceland, Sturlugata 8, Reykjavík, Iceland 
58  Geisinger Research, Biomedical and Translational Informatics Institute, Rockville, MD, USA 
59  Department of Nephrology, University Hospital Regensburg, Regensburg, Germany 
60  Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland; Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland 
61  Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore 
62  LIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany; Department of Women and Child Health, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany; Centre for Pediatric Research, University of Leipzig, Leipzig, Germany 
63  Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology and Biostatistics, University of Ulm, Ulm, Germany 
64  Integrated Research and Treatment Centre Adiposity Diseases, University of Leipzig, Leipzig, Germany 
65  Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, USA; Division of Nephrology and Hypertension, Loyola University Chicago, Chicago, IL, USA 
66  5th Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany 
67  Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria 
68  Division of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA 
69  Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland 
70  Institute of Epidemiology and Biobank Popgen, Kiel University, Kiel, Germany 
71  Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; Diabetes Centre, Khoo Teck Puat Hospital, Singapore, Singapore 
72  Cardiovascular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden 
73  Nuffield Department of Medicine, University of Oxford, Oxford, UK; Broad Institute of Harvard and MIT, Cambridge, MA, USA 
74  Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore 
75  Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK 
76  MRL, Merck & Co., Inc., Kenilworth, NJ, USA; Celgene Inc., Cambridge, MA, USA 
77  Vanderbilt University School of Medicine, Nashville, TN, USA 
78  Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany; Chair of Epidemiology Ludwig- Maximilians-Universität München at UNIKA-T Augsburg, Augsburg, Germany 
79  DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany 
80  Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Public Health and Primary Care, Leiden University Medical Centre, Leiden, The Netherlands 
81  Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany; Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU, Munich, Germany; Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Munich, Germany 
82  Centre for Public Health Genomics, University of Virginia, Charlottesville, VA, USA 
83  DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany 
84  Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, Finland; Department of Cardiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland 
85  Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA 
86  Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Centre, Leiden, The Netherlands 
87  University of Maryland School of Medicine, Baltimore, MD, USA 
88  Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland 
89  Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA 
90  DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany 
91  Service de Néphrologie, Geneva University Hospitals, Geneva, Switzerland 
92  LIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany 
93  Section of Nephrology, Department of Internal Medicine, Leiden University Medical Centre, Leiden, The Netherlands; Einthoven Laboratory of Experimental Vascular Research, Leiden University Medical Centre, Leiden, The Netherlands 
94  Department of Genetics, University of North Carolina, Chapel Hill, NC, USA 
95  Institute of Physiology, University Medicine Greifswald, Karlsburg, Germany 
96  Department of Biostatistics, University of Washington, Seattle, WA, USA 
97  Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands 
98  MRL, Merck & Co., Inc., Kenilworth, NJ, USA; Biogen Inc., Cambridge, MA, USA 
99  Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA 
100  Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore 
101  Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg, Germany 
102  Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland 
103  Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany; Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU, Munich, Germany 
104  Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany 
105  Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore 
106  The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA 
107  LIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany; Heart Centre Leipzig, Leipzig, Germany 
108  LIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany; Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany 
109  Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany 
110  Montreal University Hospital Research Centre, CHUM, Montreal, QC, Canada; CRCHUM, Montreal, QC, Canada 
111  Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands 
112  Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Durrer Centre for Cardiovascular Research, The Netherlands Heart Institute, Utrecht, The Netherlands 
113  Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 
114  DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany 
115  DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany 
116  Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 
117  Vanderbilt University Medical Centre, Division of Nephrology & Hypertension, Nashville, TN, USA 
118  Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore 
119  Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan 
120  Kidney Research Institute, University of Washington, Seattle, WA, USA; Anatomic Pathology, University of Washington Medical Center, Seattle, WA, USA 
121  Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland 
122  Department of Nephrology, University Hospital Regensburg, Regensburg, Germany; Department of Nephrology, Diabetology and Rheumatology, Kliniken Südostbayern, Traunstein, Germany 
123  Institute of Physiology, University of Zurich, Zurich, Switzerland 
124  Division of Epidemiology, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Centre, Nashville, TN, USA; Department of Veteran’s Affairs, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, USA 
125  Kidney Health Research Institute (KHRI), Geisinger, Danville, PA, USA; Department of Nephrology, Geisinger, Danville, PA, USA 
126  Department of Biostatistics, University of Liverpool, Liverpool, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK 
127  Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA 
128  Geisinger Research, Biomedical and Translational Informatics Institute, Danville, PA, USA 
129  Cardiovascular Health Research Unit, Department of Medicine, Department of Epidemiology, Department of Health Service, University of Washington, Seattle, WA, USA; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA 
130  The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA; Department of Pediatrics, Harbor-UCLA Medical Centre, Torrance, CA, USA; Department of Medicine, Harbor-UCLA Medical Centre, Torrance, CA, USA 
131  Department of Physiology and Biophysics, University of Mississippi Medical Centre, Jackson, MS, USA 
132  Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany 
133  MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK 
134  Vanderbilt University Medical Centre, Division of Nephrology & Hypertension, Nashville, TN, USA; Department of Veteran’s Affairs, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, USA 
135  Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA 
Pages
1-19
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2288675151
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.