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

Nat Commun
Authors
Cristian Pattaro
Alexander Teumer
Mathias Gorski
Audrey 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 Pers
Andrew Johnson
Yi-An Ko
Christian Fuchsberger
Bamidele Tayo
Michael Nalls
Mary Feitosa
Aaron Isaacs
Abbas Dehghan
Pio D'Adamo
Adebowale Adeyemo
Aida Dieffenbach
Alan Zonderman
Ilja Nolte
Peter van der Most
Alan Wright
Alan Shuldiner
Alanna Morrison
Albert Hofman
Albert Smith
Albert Dreisbach
Andre Franke
André Uitterlinden
Andres Metspalu
Anke Tönjes
Antonio Lupo
Antonietta Robino
Asa Johansson
Ayse Demirkan
Barbara Kollerits
Barry Freedman
Belen Ponte
Ben Oostra
Bernhard Paulweber
Bernhard Krämer
Braxton Mitchell
Brendan Buckley
Carmen Peralta
Caroline Hayward
Catherine Helmer
Charles Rotimi
Christian Shaffer
Christian Müller
Cinzia Sala
Cornelia van Duijn
Aude Saint-Pierre
Daniel Ackermann
Daniel Shriner
Daniela Ruggiero
Daniela Toniolo
Yingchang Lu
Daniele Cusi
Darina Czamara
David Ellinghaus
David Siscovick
Douglas Ruderfer
Christian Gieger
Harald Grallert
Elena Rochtchina
Elizabeth Atkinson
Elizabeth Holliday
Eric Boerwinkle
Erika Salvi
Erwin Bottinger
Federico Murgia
Fernando Rivadeneira
Florian Ernst
Florian Kronenberg
Frank Hu
Gerjan Navis
Gary Curhan
George Ehret
Georg Homuth
Stefan Coassin
Gian-Andri Thun
Giorgio Pistis
Giovanni Gambaro
Giovanni Malerba
Grant Montgomery
Gudny Eiriksdottir
Gunnar Jacobs
Guo Li
H-Erich Wichmann
Harry Campbell
Helena Schmidt
Henri Wallaschofski
Henry Völzke
Hermann Brenner
Heyo Kroemer
Holly Kramer
Honghuang Lin
I Mateo Leach
Ian Ford
Idris Guessous
Igor Rudan
Inga Prokopenko
Ingrid Borecki
Iris Heid
Ivana Kolcic
Ivana Persico
J Wouter Jukema
James Wilson
Janine Felix
Jasmin Divers
Jean-Charles Lambert
Jeanette Stafford
Jean-Michel Gaspoz
Jennifer Smith
Jessica Faul
Jie Wang
Jingzhong Ding
Joel Hirschhorn
John Attia
John Whitfield
John Chalmers
Jorma Viikari
Josef Coresh
Joshua Denny
Juha Karjalainen
Jyotika Fernandes
Karlhans Endlich
Katja Butterbach
Keith Keene
Kurt Lohman
Laura Portas
Lenore Launer
Leo-Pekka Lyytikäinen
Loic Yengo
Lude Franke
Luigi Ferrucci
Lynda Rose
Lyudmyla Kedenko
Madhumathi Rao
Maksim Struchalin
Marcus Kleber
Margherita Cavalieri
Margot Haun
Marilyn Cornelis
Marina Ciullo
Mario Pirastu
Mariza de Andrade
Mark McEvoy
Mark Woodward
Martin Adam
Massimiliano Cocca
Matthias Nauck
Medea Imboden
Melanie Waldenberger
Menno Pruijm
Marie Metzger
Michael Stumvoll
Michele Evans
Michèle Sale
Mika Kähönen
Mladen Boban
Murielle Bochud
Myriam Rheinberger
Niek Verweij
Nabila Bouatia-Naji
Nicholas Martin
Nick Hastie
Nicole Probst-Hensch
Nicole Soranzo
Olivier Devuyst
Olli Raitakari
Omri Gottesman
Oscar Franco
Ozren Polasek
Paolo Gasparini
Patricia Munroe
Paul Ridker
Paul Mitchell
Paul Muntner
Christa Meisinger
Johannes Smit
ICBP Consortium
AGEN Consortium
CARDIOGRAM
CHARGe-Heart Failure Group
EchoGen Consortium
Peter Kovacs
Philipp Wild
Philippe Froguel
Rainer Rettig
Reedik Mägi
Reiner Biffar
Reinhold Schmidt
Rita Middelberg
Robert Carroll
Brenda Penninx
Rodney Scott
Ronit Katz
Sanaz Sedaghat
Sarah Wild
Sharon Kardia
Sheila Ulivi
Shih-Jen Hwang
Stefan Enroth
Stefan Kloiber
Stella Trompet
Benedicte Stengel
Stephen Hancock
Stephen Turner
Sylvia Rosas
Sylvia Stracke
Tamara Harris
Tanja Zeller
Tatijana Zemunik
Terho Lehtimäki
Thomas Illig
Thor Aspelund
Tiit Nikopensius
Tõnu Esko
Toshiko Tanaka
Ulf Gyllensten
Uwe Volker
Valur Emilsson
Veronique Vitart
Ville Aalto
Vilmundur Gudnason
Vincent Chouraki
Wei-Min Chen
Wilmar Igl
Winfried März
Wolfgang Koenig
Wolfgang Lieb
Ruth Loos
Yongmei Liu
Harold Snieder
Peter Pramstaller
Afshin Parsa
Jeffrey O'Connell
Katalin Susztak
Pavel Hamet
Johanne Tremblay
Ian de Boer
Carsten Böger
Wolfram Goessling
Daniel Chasman
Anna Köttgen
W Kao
Caroline Fox
Keywords
Humans
Gene Expression Regulation
Genetic Predisposition to Disease
Genotype
Genome-Wide Association Study
Renal Insufficiency, Chronic
Abstract

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.
Year of Publication
2016
Journal
Nat Commun
Volume
7
Pages
10023
Date Published
2016 Jan 21
ISSN
2041-1723
URL
http://dx.doi.org/10.1038/ncomms10023
DOI
10.1038/ncomms10023
PubMed ID
26831199
PubMed Central ID
PMC4735748
Links
Grant list
R01 MD009055 / MD / NIMHD NIH HHS / United States
R01 DK058845 / DK / NIDDK NIH HHS / United States
K12 RR023250 / RR / NCRR NIH HHS / United States
R01DK090311 / DK / NIDDK NIH HHS / United States
R24 OD017870 / OD / NIH HHS / United States
DP3 DK108220 / DK / NIDDK NIH HHS / United States
R01 HL087660 / HL / NHLBI NIH HHS / United States
P30 DK079637 / DK / NIDDK NIH HHS / United States
T32 HL007024 / HL / NHLBI NIH HHS / United States
P30 DK079626 / DK / NIDDK NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
U01 HL084756 / HL / NHLBI NIH HHS / United States
R01 DK084350 / DK / NIDDK NIH HHS / United States
P30 DK072488 / DK / NIDDK NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
Z01 HG200362-01 / Intramural NIH HHS / United States
G0401527 / Medical Research Council / United Kingdom
P30 DK020541 / DK / NIDDK NIH HHS / United States
U01 HL072515 / HL / NHLBI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
FS/14/55/30806 / British Heart Foundation / United Kingdom
MR/K006584/1 / Medical Research Council / United Kingdom
MR/K013351/1 / Medical Research Council / United Kingdom
HHSN268201100009C / HL / NHLBI NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
G0600237 / Medical Research Council / United Kingdom
R01 DK066574 / DK / NIDDK NIH HHS / United States
R01 DK090311 / DK / NIDDK NIH HHS / United States
F31 AG044879 / AG / NIA NIH HHS / United States
R01 AG018728 / AG / NIA NIH HHS / United States
U01 HG004399 / HG / NHGRI NIH HHS / United States
U01 GM074518 / GM / NIGMS NIH HHS / United States
R01 HL088119 / HL / NHLBI NIH HHS / United States
R24OD017870 / OD / NIH HHS / United States

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