Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Cristian Pattaro; Alexander Teumer; Mathias Gorski; Audrey Y Chu; Man Li; Vladan Mijatovic; Maija Garnaas; Adrienne Tin; Rossella Sorice; Yong Li; Daniel Taliun; Matthias Olden; Meredith Foster; Qiong Yang; Ming-Huei Chen; Tune H Pers; Andrew D Johnson; Yi-An Ko; Christian Fuchsberger; Bamidele Tayo; Michael Nalls; Mary F Feitosa; Aaron Isaacs; Abbas Dehghan; Pio d'Adamo; Adebowale Adeyemo; Aida Karina Dieffenbach; Alan B Zonderman; Ilja M Nolte; Peter J van der Most; Alan F Wright; Alan R Shuldiner; Alanna C Morrison; Albert Hofman; Albert V Smith; Albert W Dreisbach; Andre Franke; Andre G Uitterlinden; Andres Metspalu; Anke Tonjes; Antonio Lupo; Antonietta Robino; Åsa Johansson; Ayse Demirkan; Barbara Kollerits; Barry I Freedman; Belen Ponte; Ben A Oostra; Bernhard Paulweber; Bernhard K Krämer; Braxton D Mitchell; Brendan M Buckley; Carmen A Peralta; Caroline Hayward; Catherine Helmer; Charles N Rotimi; Christian M Shaffer; Christian Müller; Cinzia Sala; Cornelia M van Duijn; Aude Saint-Pierre; Daniel Ackermann; Daniel Shriner; Daniela Ruggiero; Daniela Toniolo; Yingchang Lu; Daniele Cusi; Darina Czamara; David Ellinghaus; David S Siscovick; Douglas Ruderfer; Christian Gieger; Harald Grallert; Elena Rochtchina; Elizabeth J Atkinson; Elizabeth G Holliday; Eric Boerwinkle; Erika Salvi; Erwin P Bottinger; Federico Murgia; Fernando Rivadeneira; Florian Ernst; Florian Kronenberg; Frank B Hu; Gerjan J Navis; Gary C Curhan; George B Ehret; Georg Homuth; Stefan Coassin; Gian-Andri Thun; Giorgio Pistis; Giovanni Gambaro; Giovanni Malerba; Grant W Montgomery; Gudny Eiriksdottir; Gunnar Jacobs; Guo Li; H-Erich Wichmann; Harry Campbell; Helena Schmidt; CARDIOGRAM; Inga Prokopenko

doi:10.1038/ncomms10023

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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Cristian Pattaro, Alexander Teumer, Mathias Gorski, Audrey Y Chu, Man Li, Vladan Mijatovic, Maija Garnaas, Adrienne Tin, Rossella Sorice, Yong Li, …

Nature communications, Vol.7(1), pp.10023-10023

21/01/2016

DOI: https://doi.org/10.1038/ncomms10023

PMID: 26831199

Abstract

Gene Expression Regulation

Genetic Predisposition to Disease

Genome-Wide Association Study

Genotype

Humans

Renal Insufficiency, Chronic - genetics

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

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Title: Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
Creators: Cristian Pattaro - Eurac Research
Alexander Teumer - Universität Greifswald
Mathias Gorski - University of Regensburg
Audrey Y Chu - Brigham and Women's Hospital
Man Li - Brigham and Women's Hospital
Vladan Mijatovic - University of Verona
Maija Garnaas - Brigham and Women's Hospital
Adrienne Tin - Johns Hopkins University
Rossella Sorice - Institute of Genetics and Biophysics
Yong Li - University Medical Center Freiburg
Daniel Taliun - Eurac Research
Matthias Olden - University of Regensburg
Meredith Foster - Tufts University
Qiong Yang - Boston University
Ming-Huei Chen - Boston University School of Medicine
Tune H Pers - Boston Children's Hospital
Andrew D Johnson - Framingham Heart Study
Yi-An Ko - University of Pennsylvania
Christian Fuchsberger - Eurac Research
Bamidele Tayo - Loyola University Medical Center
Michael Nalls - National Institute on Aging
Mary F Feitosa - Washington University in St. Louis
Aaron Isaacs - Erasmus MC
Abbas Dehghan - Erasmus MC
Pio d'Adamo - University of Trieste
Adebowale Adeyemo - National Human Genome Research Institute
Aida Karina Dieffenbach - German Cancer Research Center
Alan B Zonderman - National Institute on Aging
Ilja M Nolte - University Medical Center Groningen
Peter J van der Most - University Medical Center Groningen
Alan F Wright - MRC Institute of Genetics and Molecular Medicine
Alan R Shuldiner - University of Maryland, Baltimore
Alanna C Morrison - The University of Texas Health Science Center at Houston
Albert Hofman - Erasmus MC
Albert V Smith - Icelandic Heart Association
Albert W Dreisbach - University of Mississippi
Andre Franke - Kiel University
Andre G Uitterlinden - Erasmus MC
Andres Metspalu - University of Tartu
Anke Tonjes - Leipzig University
Antonio Lupo - University of Verona
Antonietta Robino - IRCCS Materno Infantile Burlo Garofolo
Åsa Johansson - Uppsala University
Ayse Demirkan - Erasmus MC
Barbara Kollerits - Innsbruck Medical University
Barry I Freedman - Wake Forest University
Belen Ponte - Nephrology Division, Department of Specialties of Internal Medicine, Geneva University Hospital, 4 rue Gabrielle-Perret-Gentil, Geneve 1211, Switzerland
Ben A Oostra - Erasmus MC
Bernhard Paulweber - Paracelsus Medical University
Bernhard K Krämer - University Medical Centre Mannheim
Braxton D Mitchell - University of Maryland, Baltimore
Brendan M Buckley - University College Cork
Carmen A Peralta - University of California, San Francisco
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Catherine Helmer - Inserm
Charles N Rotimi - National Human Genome Research Institute
Christian M Shaffer - Vanderbilt University
Christian Müller - Universität Hamburg
Cinzia Sala - San Raffaele University of Rome
Cornelia M van Duijn - Erasmus MC
Aude Saint-Pierre - Eurac Research
Daniel Ackermann - Nephrology Division, Department of Specialties of Internal Medicine, Geneva University Hospital, 4 rue Gabrielle-Perret-Gentil, Geneve 1211, Switzerland
Daniel Shriner - National Human Genome Research Institute
Daniela Ruggiero - Institute of Genetics and Biophysics
Daniela Toniolo - San Raffaele University of Rome
Yingchang Lu - Icahn School of Medicine at Mount Sinai
Daniele Cusi - University of Milan
Darina Czamara - Max Planck Institute of Psychiatry
David Ellinghaus - Kiel University
David S Siscovick - University of Washington
Douglas Ruderfer - Icahn School of Medicine at Mount Sinai
Christian Gieger - Helmholtz Zentrum München
Harald Grallert - Helmholtz Zentrum München
Elena Rochtchina - Westmead Institute
Elizabeth J Atkinson - Mayo Clinic
Elizabeth G Holliday - University of Newcastle Australia
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Erika Salvi - University of Milan
Erwin P Bottinger - Icahn School of Medicine at Mount Sinai
Federico Murgia - Institute of Population Genetics-CNR, Traversa La Crucca 3, 07040 Reg. Baldinca, Li Punti, Sassari, Italy
Fernando Rivadeneira - Erasmus MC
Florian Ernst - Universität Greifswald
Florian Kronenberg - Innsbruck Medical University
Frank B Hu - Harvard University
Gerjan J Navis - University Medical Center Groningen
Gary C Curhan - Brigham and Women's Hospital
George B Ehret - University Hospital of Geneva
Georg Homuth - Universität Greifswald
Stefan Coassin - Innsbruck Medical University
Gian-Andri Thun - Swiss Tropical and Public Health Institute
Giorgio Pistis - San Raffaele University of Rome
Giovanni Gambaro - Agostino Gemelli University Polyclinic
Giovanni Malerba - University of Verona
Grant W Montgomery - QIMR Berghofer Medical Research Institute
Gudny Eiriksdottir - Icelandic Heart Association
Gunnar Jacobs - Kiel University
Guo Li - University of Washington
H-Erich Wichmann - Helmholtz Zentrum München
Harry Campbell - University of Edinburgh
Helena Schmidt - Medical University of Graz
CARDIOGRAM
Inga Prokopenko - School of Biosciences
Publication Details: Nature communications, Vol.7(1), pp.10023-10023
Publication Date: 21/01/2016
Grant note: K12 RR023250 / NCRR NIH HHS MR/N003284/1 / Medical Research Council U01 HG004402 / NHGRI NIH HHS R01 DK084350 / NIDDK NIH HHS P30 DK079626 / NIDDK NIH HHS F31 AG044879 / NIA NIH HHS P30 DK020541 / NIDDK NIH HHS R24 OD017870 / NIH HHS R01 DK090311 / NIDDK NIH HHS P30 DK079637 / NIDDK NIH HHS
Identifiers: 99928786702346; WOS:000369032800001
Academic Unit: School of Biosciences; Institute for Sustainability; Surrey Institute for People-Centred AI
Language: English
Resource Type: Journal article

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

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