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Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.
Morris, Andrew P; Le, Thu H; Wu, Haojia; Akbarov, Artur; van der Most, Peter J; Hemani, Gibran; Smith, George Davey; Mahajan, Anubha; Gaulton, Kyle J; Nadkarni, Girish N; Valladares-Salgado, Adan; Wacher-Rodarte, Niels; Mychaleckyj, Josyf C; Dueker, Nicole D; Guo, Xiuqing; Hai, Yang; Haessler, Jeffrey; Kamatani, Yoichiro; Stilp, Adrienne M; Zhu, Gu; Cook, James P; Ärnlöv, Johan; Blanton, Susan H; de Borst, Martin H; Bottinger, Erwin P; Buchanan, Thomas A; Cechova, Sylvia; Charchar, Fadi J; Chu, Pei-Lun; Damman, Jeffrey; Eales, James; Gharavi, Ali G; Giedraitis, Vilmantas; Heath, Andrew C; Ipp, Eli; Kiryluk, Krzysztof; Kramer, Holly J; Kubo, Michiaki; Larsson, Anders; Lindgren, Cecilia M; Lu, Yingchang; Madden, Pamela A F; Montgomery, Grant W; Papanicolaou, George J; Raffel, Leslie J; Sacco, Ralph L; Sanchez, Elena; Stark, Holger; Sundstrom, Johan; Taylor, Kent D.
Afiliação
  • Morris AP; Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, UK. apmorris@liverpool.ac.uk.
  • Le TH; Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK. apmorris@liverpool.ac.uk.
  • Wu H; Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, VA, 22908, USA.
  • Akbarov A; Division of Nephrology, Washington University School of Medicine, St Louis, MO, 63110, USA.
  • van der Most PJ; Division of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, M13 9PT, UK.
  • Hemani G; Department of Epidemiology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, Netherlands.
  • Smith GD; MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 1TH, UK.
  • Mahajan A; MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 1TH, UK.
  • Gaulton KJ; Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
  • Nadkarni GN; Department of Pediatrics, University of California, San Diego, San Diego, CA, 92161, USA.
  • Valladares-Salgado A; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Wacher-Rodarte N; Division of Nephrology and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Mychaleckyj JC; Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, 06720, Mexico.
  • Dueker ND; Unidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, 06720, Mexico.
  • Guo X; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
  • Hai Y; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33124, USA.
  • Haessler J; Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
  • Kamatani Y; Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
  • Stilp AM; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.
  • Zhu G; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
  • Cook JP; Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
  • Ärnlöv J; Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Blanton SH; Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, UK.
  • de Borst MH; Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Huddinge, 141 83, Sweden.
  • Bottinger EP; School of Health and Social Studies, Dalarna University, Falun, 791 88, Sweden.
  • Buchanan TA; John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33124, USA.
  • Cechova S; Dr John T Macdonald Department of Human Genetics, University of Miami, Miami, FL, 33124, USA.
  • Charchar FJ; Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, Netherlands.
  • Chu PL; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Damman J; Department of Medicine, Division of Endocrinology and Diabetes, Keck School of Medicine of USC, Los Angeles, CA, 90033, USA.
  • Eales J; Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, VA, 22908, USA.
  • Gharavi AG; School of Health and Life Sciences, Federation University Australia, Ballarat, VIC, 3350, Australia.
  • Giedraitis V; Department of Cardiovascular Sciences, University of Leicester, Leicester, LE1 7RH, UK.
  • Heath AC; Department of Physiology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Ipp E; Department of Internal Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City, 242, Taiwan.
  • Kiryluk K; Department of Pathology, Erasmus Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, Netherlands.
  • Kramer HJ; Division of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, M13 9PT, UK.
  • Kubo M; Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
  • Larsson A; Department of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, Uppsala, 751 85, Sweden.
  • Lindgren CM; Department of Psychiatry, Washington University in St Louis, St Louis, MO, 63110, USA.
  • Lu Y; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90024, USA.
  • Madden PAF; Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, CA, 90502, USA.
  • Montgomery GW; Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
  • Papanicolaou GJ; Department of Medicine and Nephrology, Loyola University Medical Center, Maywood, IL, 60153, USA.
  • Raffel LJ; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
  • Sacco RL; Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, 751 85, Sweden.
  • Sanchez E; Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
  • Stark H; Li Ka Shing Centre for Health Information and Discovery, Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
  • Sundstrom J; Broad Institute of Harvard and MIT, Boston, MA, 02142, USA.
  • Taylor KD; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Nat Commun ; 10(1): 29, 2019 01 03.
Article em En | MEDLINE | ID: mdl-30604766
ABSTRACT
Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cálculos Renais / Insuficiência Renal Crônica / Taxa de Filtração Glomerular / Hipertensão / Rim Idioma: En Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cálculos Renais / Insuficiência Renal Crônica / Taxa de Filtração Glomerular / Hipertensão / Rim Idioma: En Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Reino Unido