SynthesisKidney international2022
Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies.
Full text readMeta-Analysis
In one paragraph
Synthesis in Kidney international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function.Communications biology · 2023Pooled it
- Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults.Kidney international · 2023Trial
- A tri-scale in silico framework integrating pharmacovigilance and mechanistic modeling suggests tepotinib-associated acute kidney injury risk.Renal failure · 2026Article
- Genetic Variants With Small Discordant Effects on eGFR and Risk of CKD.Kidney international reports · 2026Article
- Protein mediators of chronic kidney disease in Type 2 diabetes: A mendelian randomization study.PLoS medicine · 2026Article
- Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease.Nature communications · 2026Article
- Scoping Review of Polygenic Risk Scores in Kidney-Related Traits.Kidney international reports · 2026Article
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- FEMA-Long: Modeling unstructured covariances for discovery of time-dependent effects in large-scale longitudinal datasets.PLoS genetics · 2026Article
- Low genetic risk for coronary artery disease underlies multigenerational longevity and healthy aging.GeroScience · 2026Article
- From GWAS Signals to Causal Genes in Chronic Kidney Disease.Current issues in molecular biology · 2026Review
- An application of the MR-Horse method to reduce selection bias in genome-wide association studies of disease progression.European journal of human genetics : EJHG · 2025Article
- Genome-wide polygenic risk score for estimated glomerular filtration slope predicts chronic kidney disease in a Taiwanese population.Journal of nephrology · 2025Article
- Detection of Fast Decliner of Diabetic Kidney Disease Using Chiral Amino Acid Profiling: A Pilot Study.Chemistry & biodiversity · 2025Article
- Genes, kidneys, and the future: transforming chronic kidney disease management through genomic insights.Childhood kidney diseases · 2025Review
- Risk-directed management of chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Metabolomics profiling in multi-ancestral individuals with type 2 diabetes in Singapore identified metabolites associated with renal function decline.Diabetologia · 2025Article
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- Bias-corrected serum creatinine from UK Biobank electronic medical records generates an important data resource for kidney function trajectories.Scientific reports · 2025Article
- Polygenic scores and their applications in kidney disease.Nature reviews. Nephrology · 2025Review
Corrections and comments
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Authors and funding
177 authors.
Mathias GorskiDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany; Department of Nephrology, University Hospital Regensburg, Regensburg, Germany. Electronic address: mathias.gorski@klinik.uni-regensburg.de.
Humaira RasheedK. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany; Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland.
Laurent F ThomasK. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; BioCore-Bioinformatics Core Facility, Norwegian University of Science and Technology, Trondheim, Norway.
Sarah E GrahamDepartment of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, Michigan, USA.
Gardar SveinbjornssondeCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Thomas W WinklerDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Felix GüntherDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany; Statistical Consulting Unit StaBLab, Department of Statistics, LMU Munich, Munich, Germany.
Klaus J StarkDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Jin-Fang ChaiSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Bamidele O TayoDepartment of Public Health Sciences, Loyola University Chicago, Maywood, Illinois, USA.
Matthias WuttkeInstitute 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 IV, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
Yong LiInstitute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
Adrienne TinMemory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, Mississippi, USA; Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Tarunveer S AhluwaliaSteno Diabetes Center Copenhagen, Gentofte, Denmark; The Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Johan ÄrnlövDivision of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; School of Health and Social Studies, Dalarna University, Stockholm, Sweden.
Bjørn Olav ÅsvoldK. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Stephan J L BakkerDivision of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Bernhard BanasDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Nisha BansalDivision of Nephrology, University of Washington, Seattle, Washington, USA; Kidney Research Institute, University of Washington, Seattle, Washington, USA.
Mary L BiggsCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA; Department of Biostatistics, University of Washington, Seattle, Washington, USA.
Ginevra BiinoInstitute of Molecular Genetics, National Research Council of Italy, Pavia, Italy.
Michael BöhnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Eric BoerwinkleHuman Genetics Center, University of Texas Health Science Center, Houston, Texas, USA.
Erwin P BottingerCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Digital Health Center, Hasso Plattner Institute and University of Potsdam, Potsdam, Germany.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Network Aging Research, Heidelberg University, Heidelberg, Germany.
Ben BrumptonK. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; Clinic of Thoracic and Occupational Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Robert J CarrollDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Layal ChakerDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
John ChalmersThe George Institute for Global Health, University of New South Wales, Sydney, Australia.
Miao-Li CheeSingapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.
Miao-Ling CheeSingapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.
Ching-Yu ChengSingapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; Ophthalmology and 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.
Audrey Y ChuGenetics, Merck & Co, Inc., Kenilworth, New Jersey, USA.
Marina CiulloInstitute of Genetics and Biophysics "Adriano Buzzati-Traverso"-CNR, Naples, Italy; IRCCS Neuromed, Pozzilli, Italy.
Massimiliano CoccaInstitute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste, Italy.
James P CookDepartment of Health Data Science, University of Liverpool, Liverpool, UK.
Josef CoreshDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Daniele CusiInstitute of Biomedical Technologies, National Research Council of Italy, Milan, Italy; Bio4Dreams-Business Nursery for Life Sciences, Milan, Italy.
Martin H de BorstDivision of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Frauke DegenhardtInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Kai-Uwe EckardtDepartment of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Nephrology and Hypertension, Friedrich Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Karlhans EndlichDZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany; Department of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany.
Michele K EvansLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, US National Institutes of Health, Baltimore, Maryland, USA.
Mary F FeitosaDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Sandra Freitag-WolfInstitute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein, Kiel, Germany.
Christian FuchsbergerDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA; Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.
Piyush GampawarInstitute of Molecular Biology and Biochemistry, Center for Molecular Medicine, Medical University of Graz, Graz, Austria.
Ron T GansevoortDivision of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Mohsen GhanbariDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Sahar GhasemiInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
Vilmantas GiedraitisMolecular Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
Christian GiegerResearch Unit Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
Daniel F GudbjartssondeCODE Genetics/Amgen, Inc., Reykjavik, Iceland; Iceland School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
Stein HallanDepartment of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Nephrology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Pavel HametMontreal University Hospital Research Center, CHUM, Montreal, Quebec, Canada; Medpharmgene, Montreal, Quebec, Canada; CRCHUM, Montreal, Quebec, Canada.
Asahi HishidaDepartment of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kevin HoKidney Health Research Institute (KHRI), Geisinger, Danville, Pennsylvania, USA; Department of Nephrology, Geisinger, Danville, Pennsylvania, USA.
Edith HoferClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
Bernd HolleczekDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Hilma HolmdeCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Anselm HoppmannInstitute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
Katrin HornInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Nina Hutri-KähönenDepartment of Pediatrics, Tampere University Hospital, Tampere, Finland; Department of Pediatrics, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Kristian HveemK. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Shih-Jen HwangNational Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
M Arfan IkramDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Navya Shilpa JosyulaGeisinger Research, Biomedical and Translational Informatics Institute, Rockville, Maryland, USA.
Bettina JungDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany; Department of Nephrology and Rheumatology, Kliniken Südostbayern, Traunstein, Germany; KfH Kidney Centre Traunstein, Traunstein, Germany.
Mika KähönenDepartment 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.
Irma KarabegovićDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Chiea-Chuen KhorSingapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.
Wolfgang KoenigDeutsches Herzzentrum München, Technische Universität München, Munich, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.
Holly KramerDepartment of Public Health Sciences, Loyola University Chicago, Maywood, Illinois, USA; Division of Nephrology and Hypertension, Loyola University Chicago, Chicago, Illinois, USA.
Bernhard K KrämerDepartment of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Brigitte KühnelResearch Unit Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Johanna KuusistoDepartment of Medicine, Kuopio University Hospital, Kuopio, Finland; Centre for Medicine and Clinical Research, University of Eastern Finland School of Medicine, Kuopio, Finland.
Markku LaaksoDepartment of Medicine, Kuopio University Hospital, Kuopio, Finland; Centre for Medicine and Clinical Research, University of Eastern Finland School of Medicine, Kuopio, Finland.
Leslie A LangeDivision of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado, USA.
Terho LehtimäkiDepartment 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.
Man LiDivision of Nephrology and Hypertension, Department of Medicine, University of Utah, Salt Lake City, Utah, USA.
Wolfgang LiebInstitute of Epidemiology and Biobank Popgen, Kiel University, Kiel, Germany.
Lifelines Cohort Study
Lars LindDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Cecilia M LindgrenNuffield Department of Population Health, University of Oxford, Oxford, UK; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA; Wellcome Center for Human Genetics, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, UK; Li Ka Shing Centre for Health Information and Discovery, The Big Data Institute, University of Oxford, Oxford, UK.
Ruth J F LoosCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Mary Ann LukasClinical Sciences, GlaxoSmithKline, Albuquerque, New Mexico, USA.
Leo-Pekka LyytikäinenDepartment 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.
Anubha MahajanWellcome Center for Human Genetics, University of Oxford, Oxford, UK; Oxford Center for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Pamela R Matias-GarciaResearch Unit Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; TUM School of Medicine, Technical University of Munich, Munich, Germany.
Christa MeisingerIndependent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Augsburg, Germany.
Thomas MeitingerDZHK (German Center 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.
Olle MelanderHypertension and Cardiovascular Disease, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Yuri MilaneschiDepartment of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC/Vrije Universiteit and GGZ inGeest, Amsterdam, the Netherlands.
Pashupati P MishraDepartment 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.
Nina MononenDepartment 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.
Andrew P MorrisDepartment of Health Data Science, University of Liverpool, Liverpool, UK; Wellcome Center for Human Genetics, University of Oxford, Oxford, UK; Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK.
Josyf C MychaleckyjCenter for Public Health Genomics, University of Virginia, Charlottesville, Charlottesville, Virginia, USA.
Girish N NadkarniCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Mariko NaitoDepartment of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Masahiro NakatochiPublic Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Mike A NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA; Data Tecnica International, Glen Echo, Maryland, USA.
Matthias NauckDZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Kjell NikusDepartment 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.
Boting NingDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Ilja M NolteDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Teresa NutileInstitute of Genetics and Biophysics "Adriano Buzzati-Traverso"-CNR, Naples, Italy.
Michelle L O'DonoghueCardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA; TIMI Study Group, Boston, Massachusetts, USA.
Jeffrey O'ConnellUniversity of Maryland School of Medicine, Baltimore, Maryland, USA.
Isleifur OlafssonDepartment of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.
Marju Orho-MelanderDiabetes and Cardiovascular Disease-Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
Afshin ParsaDivision of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Sarah A PendergrassGeisinger Research, Biomedical and Translational Informatics Institute, Danville, Pennsylvania, USA.
Brenda W J H PenninxDepartment of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC/Vrije Universiteit and GGZ inGeest, Amsterdam, the Netherlands.
Mario PirastuInstitute of Genetic and Biomedical Research, National Research Council of Italy, UOS of Sassari, Li Punti, Sassari, Italy.
Michael H PreussCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, Department of Epidemiology, Department of Health Services, University of Washington, Seattle, Washington, USA.
Laura M RaffieldDepartment of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
Olli T RaitakariCentre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland; Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Myriam RheinbergerDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany; Department of Nephrology and Rheumatology, Kliniken Südostbayern, Traunstein, Germany; KfH Kidney Centre Traunstein, Traunstein, Germany.
Kenneth M RiceDepartment of Biostatistics, University of Washington, Seattle, Washington, USA.
Federica RizziDepartment of Health Sciences, University of Milan, Milano, Italy; ePhood Scientific Unit, ePhood SRL, Milano, Italy.
Alexander R RosenkranzDivision of Nephrology, Department of Internal Medicine, Medical University Graz, Graz, Austria.
Peter RossingSteno Diabetes Center Copenhagen, Gentofte, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
Daniela RuggieroInstitute of Genetics and Biophysics "Adriano Buzzati-Traverso"-CNR, Naples, Italy; IRCCS Neuromed, Pozzilli, Italy.
Kathleen A RyanDivision of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Charumathi SabanayagamSingapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
Erika SalviDepartment of Health Sciences, University of Milan, Milano, Italy; Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milan, Italy.
Helena SchmidtInstitute of Molecular Biology and Biochemistry, Center for Molecular Medicine, Medical University of Graz, Graz, Austria.
Reinhold SchmidtClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
Markus ScholzInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Ben SchöttkerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Network Aging Research, Heidelberg University, Heidelberg, Germany.
Christina-Alexandra SchulzDiabetes and Cardiovascular Disease-Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
Sanaz SedaghatDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
Christian M ShafferDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Karsten B SieberHuman Genetics, GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Xueling SimSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Mario SimsDepartment of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Kira J StanzickDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Unnur ThorsteinsdottirdeCODE Genetics/Amgen, Inc., Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Hannah StockerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Network Aging Research, Heidelberg University, Heidelberg, Germany.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Chair of Genetic Epidemiology, IBE, Faculty of Medicine, Ludwig-Maximilians-Universität München, München, Germany; Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
Heather M StringhamDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Patrick SulemdeCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Silke SzymczakInstitute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein, Kiel, Germany; Institute of Medical Biometry and Statistics, University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
Chris H L ThioDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Johanne TremblayMontreal University Hospital Research Center, CHUM, Montreal, Quebec, Canada; CRCHUM, Montreal, Quebec, Canada; Medpharmgene, Montreal, Quebec, Canada.
Simona VaccargiuInstitute of Genetic and Biomedical Research, National Research Council of Italy, UOS of Sassari, Li Punti, Sassari, Italy.
Pim van der HarstDepartment 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 Center for Cardiovascular Research, The Netherlands Heart Institute, Utrecht, the Netherlands.
Peter J van der MostDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Niek VerweijDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Uwe VölkerDZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Kenji WakaiDepartment of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Melanie WaldenbergerResearch Unit Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
Lars WallentinCardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Stefan WallnerInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
Judy WangDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
Dawn M WaterworthHuman Genetics, GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Harvey D WhiteGreen Lane Cardiovascular Service, Auckland City Hospital and University of Auckland, Auckland, New Zealand.
Cristen J WillerDepartment of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, Michigan, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Tien-Yin WongSingapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
Mark WoodwardThe George Institute for Global Health, University of New South Wales, Sydney, Australia; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; The George Institute for Global Health, University of Oxford, Oxford, UK.
Qiong YangDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Laura M Yerges-ArmstrongHuman Genetics, GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Martina ZimmermannDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Alan B ZondermanLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, US National Institutes of Health, Baltimore, Maryland, USA.
Tobias BerglerDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Kari StefanssondeCODE Genetics/Amgen, Inc., Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Carsten A BögerDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany; Department of Nephrology and Rheumatology, Kliniken Südostbayern, Traunstein, Germany; KfH Kidney Centre Traunstein, Traunstein, Germany.
Cristian PattaroEurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.
Anna KöttgenInstitute 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, Maryland, USA.
Florian KronenbergInstitute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Iris M HeidDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany. Electronic address: iris.heid@klinik.uni-regensburg.de.
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8MHealthy Aging In Neighborhoods of Diversity Across the Life Span (HANDLS)ZIAAG000513 · NIA · NATIONAL INSTITUTE ON AGING · PI EVANS, MICHELE K · 2009 to 2025
$70.9MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MVANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7MThe Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MGenome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2MZonulin Antibodies in Intestinal Permeabilitiy in IDDMM01RR016500 · NCRR · UNIVERSITY OF MARYLAND BALTIMORE · PI EDELMAN, MARTIN J. · 2002 to 2009
$20.2MPharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4MResearch BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D · 2005 to 2019
$17.3MIntramural NIH HHS Z01 AG000513Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NCATS NIH HHS KL2 TR002490NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001881NCI NIH HHS T32 CA160056NCRR NIH HHS K12 RR023250NCRR NIH HHS M01 RR016500NCRR NIH HHS S10 RR025141NCRR NIH HHS UL1 RR024975NCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01 HG004798NHGRI NIH HHS U01 HG006378NHGRI NIH HHS U01 HG007417NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS 75N92021D00006NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS HHSN268201800010INHLBI NIH HHS HHSN268201800011INHLBI NIH HHS HHSN268201800013INHLBI NIH HHS HHSN268201800014INHLBI NIH HHS HHSN268201800015INHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL088119NHLBI NIH HHS R35 HL135824NHLBI NIH HHS T32 HL129982NHLBI NIH HHS U01 HL072515NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL084756NHLBI NIH HHS U01 HL130114NHLBI NIH HHS U19 HL065962NIA NIH HHS R01 AG018728NIA NIH HHS R01 AG023629NICHD NIH HHS P50 HD104224NICHD NIH HHS R01 HD074711NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK072488NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK101855NIDDK NIH HHS R01 DK107786NIDDK NIH HHS R01 DK110113NIGMS NIH HHS P50 GM115305NIGMS NIH HHS RC2 GM092618NIGMS NIH HHS U01 GM074518NIH HHS S10 OD026880NIH HHS S10 OD030463NIMH NIH HHS R01 MH081802NIMH NIH HHS RC2 MH089951NIMH NIH HHS RC2 MH089995NINDS NIH HHS R01 NS032830NLM NIH HHS R01 LM010098
Abstract
Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
Indexed as
N-AcetylgalactosaminyltransferasesRenal InsufficiencyRenal Insufficiency, ChronicCross-Sectional StudiesGenetic LociGenome-Wide Association StudyGlomerular Filtration RateHumansKidneyLongitudinal StudiesGALNTL5 protein, humanN-Acetylgalactosaminyltransferasesacute kidney injurychronic kidney diseasediabetesgene expression
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