Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30604766
TITLE
Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.
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.
DATE PUBLISHED
2019 Jan 03
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2018/08/16
accepted 2018/12/03
entrez 2019/01/04 06:00
pubmed 2019/01/04 06:00
medline 2019/01/04 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Morris AP Morris Andrew P AP Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK. apmorris@liverpool.ac.uk.
Le TH Le Thu H TH Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, VA, 22908, USA.
Wu H Wu Haojia H Division of Nephrology, Washington University School of Medicine, St Louis, MO, 63110, USA.
Akbarov A Akbarov Artur A Division of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, M13 9PT, UK.
van der Most PJ van der Most Peter J PJ Department of Epidemiology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, Netherlands.
Hemani G Hemani Gibran G MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 1TH, UK.
Smith GD Smith George Davey GD MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 1TH, UK.
Mahajan A Mahajan Anubha A Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Gaulton KJ Gaulton Kyle J KJ Department of Pediatrics, University of California, San Diego, San Diego, CA, 92161, USA.
Nadkarni GN Nadkarni Girish N GN Division of Nephrology and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Valladares-Salgado A Valladares-Salgado Adan A Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, 06720, Mexico.
Wacher-Rodarte N Wacher-Rodarte Niels N Unidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, 06720, Mexico.
Mychaleckyj JC Mychaleckyj Josyf C JC Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Dueker ND Dueker Nicole D ND John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33124, USA.
Guo X Guo Xiuqing X 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.
Hai Y Hai Yang 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.
Haessler J Haessler Jeffrey J Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.
Kamatani Y Kamatani Yoichiro Y Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
Stilp AM Stilp Adrienne M AM Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
Zhu G Zhu Gu G Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Cook JP Cook James P JP Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, UK.
Ärnlöv J Ärnlöv Johan J School of Health and Social Studies, Dalarna University, Falun, 791 88, Sweden.
Blanton SH Blanton Susan H SH Dr John T Macdonald Department of Human Genetics, University of Miami, Miami, FL, 33124, USA.
de Borst MH de Borst Martin H MH Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, Netherlands.
Bottinger EP Bottinger Erwin P EP Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Buchanan TA Buchanan Thomas A TA Department of Medicine, Division of Endocrinology and Diabetes, Keck School of Medicine of USC, Los Angeles, CA, 90033, USA.
Cechova S Cechova Sylvia S Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, VA, 22908, USA.
Charchar FJ Charchar Fadi J FJ Department of Physiology, University of Melbourne, Parkville, VIC, 3010, Australia.
Chu PL Chu Pei-Lun PL Department of Internal Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City, 242, Taiwan.
Damman J Damman Jeffrey J Department of Pathology, Erasmus Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, Netherlands.
Eales J Eales James J Division of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, M13 9PT, UK.
Gharavi AG Gharavi Ali G AG Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Giedraitis V Giedraitis Vilmantas V Department of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, Uppsala, 751 85, Sweden.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University in St Louis, St Louis, MO, 63110, USA.
Ipp E Ipp Eli E Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, CA, 90502, USA.
Kiryluk K Kiryluk Krzysztof K Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Kramer HJ Kramer Holly J HJ Department of Medicine and Nephrology, Loyola University Medical Center, Maywood, IL, 60153, USA.
Kubo M Kubo Michiaki M Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
Larsson A Larsson Anders A Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, 751 85, Sweden.
Lindgren CM Lindgren Cecilia M CM Broad Institute of Harvard and MIT, Boston, MA, 02142, USA.
Lu Y Lu Yingchang Y Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Madden PAF Madden Pamela A F PAF Department of Psychiatry, Washington University in St Louis, St Louis, MO, 63110, USA.
Montgomery GW Montgomery Grant W GW Brisbane Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.
Papanicolaou GJ Papanicolaou George J GJ Epidemiology Branch, Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD, 20892, USA.
Raffel LJ Raffel Leslie J LJ Department of Pediatrics, Division of Genetic and Genomic Medicine, University of California, Irvine Orange, CA, 92868, USA.
Sacco RL Sacco Ralph L RL Jackson Memorial Hospital, University of Miami, Miami, FL, 33136-1096, USA.
Sanchez E Sanchez Elena E Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Stark H Stark Holger H Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany.
Sundstrom J Sundstrom Johan J Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, 751 85, Sweden.
Taylor KD Taylor Kent D KD 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.
Xiang AH Xiang Anny H AH Department of Research and Education, Kaiser Permanente Southern California, Pasadena, CA, 91101, USA.
Zivkovic A Zivkovic Aleksandra A Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany.
Lind L Lind Lars L Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, 751 85, Sweden.
Ingelsson E Ingelsson Erik E Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 751 85, Sweden.
Martin NG Martin Nicholas G NG Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Whitfield JB Whitfield John B JB Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Cai J Cai Jianwen J Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7420, USA.
Laurie CC Laurie Cathy C CC Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
Okada Y Okada Yukinori Y Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Suita, 565-0871, Japan.
Matsuda K Matsuda Koichi K Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
Kooperberg C Kooperberg Charles C Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.
Chen YI Chen Yii-Der Ida YI 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.
Rundek T Rundek Tatjana T Evelyn F McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Rich SS Rich Stephen S SS Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Loos RJF Loos Ruth J F RJF Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Parra EJ Parra Esteban J EJ Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, L5L 1C6, Canada.
Cruz M Cruz Miguel M Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, 06720, Mexico.
Rotter JI Rotter Jerome I JI 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.
Snieder H Snieder Harold H Department of Epidemiology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, Netherlands.
Tomaszewski M Tomaszewski Maciej M Division of Medicine, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK.
Humphreys BD Humphreys Benjamin D BD Division of Nephrology, Washington University School of Medicine, St Louis, MO, 63110, USA.
Franceschini N Franceschini Nora N Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27516-8050, USA. noraf@unc.edu.
INVESTIGATORS
JOURNAL
VOLUME: 10
ISSUE: 1
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2019
MONTH: Jan
DAY: 03
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
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Journal Article
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