A catalog of genetic loci associated with kidney function from analyses of a million individuals
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, metaanalýza, práce podpořená grantem
Grantová podpora
R01 DK093757
NIDDK NIH HHS - United States
R01 HL120393
NHLBI NIH HHS - United States
RG/13/13/30194
British Heart Foundation - United Kingdom
U01 HL130114
NHLBI NIH HHS - United States
S10 OD023680
NIH HHS - United States
U01 AG023746
NIA NIH HHS - United States
P30 DK020572
NIDDK NIH HHS - United States
P30 DK116074
NIDDK NIH HHS - United States
R01 HL117078
NHLBI NIH HHS - United States
RG/18/13/33946
British Heart Foundation - United Kingdom
Z01 AG000513-08
Intramural NIH HHS - United States
U01 HL120393
NHLBI NIH HHS - United States
212945/Z/18/Z
Wellcome Trust - United Kingdom
Z99 AG999999
Intramural NIH HHS - United States
R01 DK072193
NIDDK NIH HHS - United States
R01 DK062370
NIDDK NIH HHS - United States
R01 HL105756
NHLBI NIH HHS - United States
T32 HL129982
NHLBI NIH HHS - United States
MR/R023484/1
Medical Research Council - United Kingdom
R01 HL088215
NHLBI NIH HHS - United States
K12 HD043483
NICHD NIH HHS - United States
MC_UU_00007/10
Medical Research Council - United Kingdom
U01 DK062370
NIDDK NIH HHS - United States
PubMed
31152163
PubMed Central
PMC6698888
DOI
10.1038/s41588-019-0407-x
PII: 10.1038/s41588-019-0407-x
Knihovny.cz E-zdroje
- MeSH
- běloši MeSH
- celogenomová asociační studie MeSH
- chronická renální insuficience genetika patofyziologie moč MeSH
- fenotyp MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie metody MeSH
- hodnoty glomerulární filtrace MeSH
- jednonukleotidový polymorfismus MeSH
- kvantitativní znak dědičný * MeSH
- lidé MeSH
- lokus kvantitativního znaku * MeSH
- mapování chromozomů MeSH
- typy dědičnosti MeSH
- uromodulin moč MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Názvy látek
- uromodulin MeSH
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.
Anatomic Pathology University of Washington Medical Center Seattle WA USA
Beijing Tongren Eye Center Beijing Tongren Hospital Capital Medical University Beijing China
Bio4Dreams Business Nursery for Life Sciences Milan Italy
Biochemistry Wake Forest School of Medicine Winston Salem NC USA
Broad Institute of Harvard and MIT Cambridge MA USA
Cardiology Department of Medical Sciences Uppsala University Uppsala Sweden
Cardiology Geneva University Hospitals Geneva Switzerland
Cardiovascular Division Brigham and Women's Hospital Boston MA USA
Cardiovascular Epidemiology Department of Medical Sciences Uppsala University Uppsala Sweden
Cardiovascular Health Research Unit Department of Medicine University of Washington Seattle WA USA
Center for Cognitive Ageing and Cognitive Epidemiology University of Edinburgh Edinburgh UK
Center for Pediatric Research University of Leipzig Leipzig Germany
Center for Public Health Genomics University of Virginia Charlottesville Charlottesville VA USA
Chair of Epidemiology Ludwig Maximilians Universität München at UNIKA T Augsburg Augsburg Germany
Clinical Division of Neurogeriatrics Department of Neurology Medical University of Graz Graz Austria
Data Tecnica International Glen Echo MD USA
Dementia Research Institute Imperial College London London UK
Department of Anatomy and Cell Biology University Medicine Greifswald Greifswald Germany
Department of Biomedical Informatics Harvard Medical School Boston MA USA
Department of Biomedical Informatics Vanderbilt University Medical Center Nashville TN USA
Department of Biostatistics Boston University School of Public Health Boston MA USA
Department of Biostatistics Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
Department of Biostatistics University of Liverpool Liverpool UK
Department of Biostatistics University of Washington Seattle WA USA
Department of Cardiology Ealing Hospital Middlesex UK
Department of Cardiology Heart Center Tampere University Hospital Tampere Finland
Department of Cardiology Södersjukhuset Stockholm Sweden
Department of Clinical Biochemistry Landspitali University Hospital Reykjavik Iceland
Department of Clinical Chemistry Fimlab Laboratories Tampere Finland
Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands
Department of Clinical Physiology and Nuclear Medicine Turku University Hospital Turku Finland
Department of Clinical Physiology Tampere University Hospital Tampere Finland
Department of Clinical Science and Education Karolinska Institutet Södersjukhuset Stockholm Sweden
Department of Computational Biology University of Lausanne Lausanne Switzerland
Department of Endocrinology and Nephrology University of Leipzig Leipzig Germany
Department of Epidemiology Erasmus MC University Medical Center Rotterdam Rotterdam the Netherlands
Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
Department of Genetic Epidemiology University of Regensburg Regensburg Germany
Department of Genetics University of North Carolina Chapel Hill NC USA
Department of Genomics of Common Disease Imperial College London London UK
Department of Health Sciences University of Milan Milano Italy
Department of Hygiene and Epidemiology University of Ioannina Medical School Ioannina Greece
Department of Integrative Biomedical Sciences University of Cape Town Cape Town South Africa
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Medicine 2 Charles University Prague 1st Faculty of Medicine Prague Czech Republic
Department of Medicine Harbor UCLA Medical Center Torrance CA USA
Department of Medicine Kuopio University Hospital Kuopio Finland
Department of Medicine Medical Faculty Mannheim University of Heidelberg Mannheim Germany
Department of Medicine Surgery and Health Sciences University of Trieste Trieste Italy
Department of Medicine University of Maryland School of Medicine Baltimore MD USA
Department of Nephrology and Rheumatology Kliniken Südostbayern Regensburg Germany
Department of Nephrology Geisinger Danville PA USA
Department of Nephrology University Hospital Regensburg Regensburg Germany
Department of Neurology College of Physicians and Surgeons Columbia University New York NY USA
Department of Ophthalmology Graduate School of Medical Sciences Kyushu University Fukuoka Japan
Department of Ophthalmology Medical Faculty Mannheim University Heidelberg Mannheim Germany
Department of Ophthalmology Tohoku University Graduate School of Medicine Miyagi Japan
Department of Pediatrics Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
Department of Pediatrics Faculty of Medicine and Life Sciences University of Tampere Tampere Finland
Department of Pediatrics Harbor UCLA Medical Center Torrance CA USA
Department of Pediatrics Tampere University Hospital Tampere Finland
Department of Physiology and Biophysics University of Mississippi Medical Center Jackson MS USA
Department of Psychiatry University Hospital of Lausanne Lausanne Switzerland
Department of Psychiatry VU University Medical Center Amsterdam the Netherlands
Department of Public Health and Primary Care Leiden University Medical Center Leiden the Netherlands
Department of Public Health and Primary Care University of Cambridge Cambridge UK
Department of Public Health Sciences Loyola University Chicago Maywood IL USA
Department of Statistical Genetics Osaka University Graduate School of Medicine Osaka Japan
Department of Translational Research in Psychiatry Max Planck Institute of Psychiatry Munich Germany
Deutsches Herzzentrum München Technische Universität München Munich Germany
Diabetes and Obesity Research Program University of Helsinki Helsinki Finland
Diabetes Center Khoo Teck Puat Hospital Singapore Singapore
Digital Health Center Hasso Plattner Institute and University of Potsdam Potsdam Germany
Division of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg Germany
Division of Nephrology and Hypertension Department of Medicine University of Utah Salt Lake City USA
Division of Nephrology and Hypertension Loyola University Chicago Chicago IL USA
Division of Nephrology University of Washington Seattle WA USA
Division of Preventive Medicine Brigham and Women's Hospital Boston MA USA
Duke NUS Medical School Singapore Singapore
Durrer Center for Cardiovascular Research The Netherlands Heart Institute Utrecht the Netherlands
DZHK partner site Greifswald Greifswald Germany
DZHK Partner Site Munich Heart Alliance Munich Germany
eCODE Genetics Amgen Inc Reykjavik Iceland
ePhood Scientific Unit ePhood SRL Milano Italy
Estonian Genome Center Institute of Genomics University of Tartu Tartu Estonia
Eurac Research Institute for Biomedicine Bolzano Italy
Faculty of Medicine School of Health Sciences University of Iceland Reykjavik Iceland
Faculty of Medicine University of Split Split Croatia
Geisinger Research Biomedical and Translational Informatics Institute Danville PA USA
Geisinger Research Biomedical and Translational Informatics Institute Rockville MD USA
Generation R Study Group Erasmus MC University Medical Center Rotterdam Rotterdam the Netherlands
Genetics Merck and Co Inc Kenilworth NJ USA
Genome Institute of Singapore Agency for Science Technology and Research Singapore Singapore
German Center for Diabetes Research Neuherberg Germany
Gertrude H Sergievsky Center Columbia University Medical Center New York NY USA
Harvard Medical School Boston MA USA
Health Data Research UK London London UK
Heart Center Leipzig Leipzig Germany
Human Genetics Center University of Texas Health Science Center Houston TX USA
Human Genetics Wellcome Sanger Institute Hinxton UK
Icelandic Heart Association Kopavogur Iceland
Imperial College Healthcare NHS Trust Imperial College London London UK
Imperial College NIHR Biomedical Research Center Imperial College London London UK
Institute for Community Medicine University Medicine Greifswald Greifswald Germany
Institute for Maternal and Child Health IRCCS 'Burlo Garofolo' Trieste Italy
Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany
Institute for Molecular Bioscience University of Queensland St Lucia Queensland Australia
Institute of Biomedical Technologies National Research Council of Italy Milan Italy
Institute of Cardiovascular and Medical Sciences University of Glasgow Glasgow UK
Institute of Clinical Medicine Internal Medicine University of Eastern Finland Kuopio Finland
Institute of Clinical Molecular Biology Christian Albrechts University of Kiel Kiel Germany
Institute of Epidemiology and Biobank Popgen Kiel University Kiel Germany
Institute of Epidemiology and Biostatistics University of Ulm Ulm Germany
Institute of Genetics and Biophysics 'Adriano Buzzati Traverso' CNR Naples Italy
Institute of Human Genetics Helmholtz Zentrum München Neuherberg Germany
Institute of Human Genetics Technische Universität München Munich Germany
Institute of Molecular Genetics National Research Council of Italy Pavia Italy
Institute of Physiology University Medicine Greifswald Karlsburg Germany
Institute of Physiology University of Zurich Zurich Switzerland
Institute of Public Health and Social Sciences Khyber Medical University Peshawar Pakistan
Institute of Social and Preventive Medicine Lausanne University Hospital Lausanne Switzerland
Institute of Social and Preventive Medicine University of Bern Bern Switzerland
Integrated Research and Treatment Center Adiposity Diseases University of Leipzig Leipzig Germany
Intensive Care Medicine Charité Berlin Germany
Internal Medicine Department of Medicine Lausanne University Hospital Lausanne Switzerland
Kaiser Permanente Washington Health Research Institute Seattle WA USA
Kidney Health Research Institute Geisinger Danville PA USA
Kidney Research Institute University of Washington Seattle WA USA
Laboratory for Statistical Analysis RIKEN Center for Integrative Medical Sciences Osaka Japan
Laboratory for Statistical Analysis RIKEN Center for Integrative Medical Sciences Yokohama Japan
Lee Kong Chian School of Medicine Nanyang Technological University Singapore Singapore
LIFE Research Center for Civilization Diseases University of Leipzig Leipzig Germany
Max Planck Institute of Psychiatry Munich Germany
Medical Clinic 5 Medical Faculty Mannheim University of Heidelberg Mannheim Germany
Medpharmgene Montreal Quebec Canada
Montreal University Hospital Research Center CHUM Montreal Quebec Canada
MRC PHE Center for Environment and Health School of Public Health Imperial College London London UK
National Heart and Lung Institute Imperial College London London UK
National Institute for Health and Welfare Helsinki Finland
Network Aging Research University of Heidelberg Heidelberg Germany
Neuroalgology Unit Fondazione IRCCS Istituto Neurologico 'Carlo Besta' Milan Italy
NHLBI's Framingham Heart Study Framingham MA USA
NHS Blood and Transplant Cambridge UK
Nuffield Department of Medicine University of Oxford Oxford UK
Oxford Center for Diabetes Endocrinology and Metabolism University of Oxford Oxford UK
Public Health Sciences Biostatistics Wake Forest School of Medicine Winston Salem NC USA
QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
Research Center of Applied and Preventive Cardiovascular Medicine University of Turku Turku Finland
RIKEN Center for Integrative Medical Sciences Japan
San Raffaele Research Institute Milan Italy
School of Health and Social Studies Dalarna University Stockholm Sweden
School of Public Health and Community Medicine Hebrew University of Jerusalem Jerusalem Israel
Section on Nephrology Internal Medicine Wake Forest School of Medicine Winston Salem NC USA
Service de Néphrologie Geneva University Hospitals Geneva Switzerland
Shanghai Industrial Technology Institute Shanghai China
Singapore Eye Research Institute Singapore National Eye Center Singapore Singapore
Stanford Cardiovascular Institute Stanford University Stanford CA USA
Stanford Diabetes Research Center Stanford University Stanford CA USA
Steno Diabetes Center Copenhagen Gentofte Denmark
Swiss Institute of Bioinformatics Lausanne Switzerland
Synlab Academy Synlab Holding Deutschland GmbH Mannheim Germany
Target Sciences Genetics GlaxoSmithKline Albuquerque NM USA
Target Sciences Genetics GlaxoSmithKline Collegeville PA USA
The Center for Population Studies NHLBI Framingham MA USA
The Center of Public Health Sciences University of Iceland Reykjavík Iceland
The Department of Public Health Solutions National Institute for Health and Welfare Helsinki Finland
TIMI Study Group Boston MA USA
University of Maryland School of Medicine Baltimore MD USA
Uppsala Clinical Research Center Uppsala University Uppsala Sweden
Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville TN USA
Vanderbilt University Medical Center Division of Nephrology and Hypertension Nashville TN USA
Welch Center for Prevention Epidemiology and Clinical Research Baltimore MD USA
Wellcome Trust Center for Human Genetics University of Oxford Oxford UK
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Disrupted uromodulin trafficking is rescued by targeting TMED cargo receptors
An intermediate-effect size variant in UMOD confers risk for chronic kidney disease
Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
