Genome-wide association study of kidney function decline in individuals of European descent

Mathias Gorski; Adrienne Tin; Maija Garnaas; Gearoid M McMahon; Audrey Y Chu; Bamidele O Tayo; Cristian Pattaro; Alexander Teumer; Daniel I Chasman; John Chalmers; Pavel Hamet; Johanne Tremblay; Marc Woodward; Thor Aspelund; Gudny Eiriksdottir; Vilmundur Gudnason; Tamara B Harris; Lenore J Launer; Albert V Smith; Braxton D Mitchell; Jeffrey R O'Connell; Alan R Shuldiner; Josef Coresh; Man Li; Paul Freudenberger; Edith Hofer; Helena Schmidt; Reinhold Schmidt; Elizabeth G Holliday; Paul Mitchell; Jie Jin Wang; Ian H de Boer; Guo Li; David S Siscovick; Zoltan Kutalik; Tanguy Corre; Peter Vollenweider; Gerard Waeber; Jayanta Gupta; Peter A Kanetsky; Shih-Jen Hwang; Matthias Olden; Qiong Yang; Mariza de Andrade; Elizabeth J Atkinson; Sharon L. R Kardia; Stephen T Turner; Jeanette M Stafford; Jingzhong Ding; Yongmei Liu; Cristina Barlassina; Daniele Cusi; Erika Salvi; Jan A Staessen; Paul M Ridker; Harald Grallert; Christa Meisinger; Martina Mueller-Nurasyid; Bernhard K Kraemer; Holly Kramer; Sylvia E Rosas; Ilja M Nolte; Brenda W Penninx; Harold Snieder; M. Fabiola Del Greco; Andre Franke; Ute Noethlings; Wolfgang Lieb; Stephan J. L Bakker; Ron T Gansevoort; Pim van der Harst; Abbas Dehghan; Oscar H Franco; Albert Hofman; Fernando Rivadeneira; Sanaz Sedaghat; Andre G Uitterlinden; Stefan Coassin; Margot Haun; Barbara Kollerits; Florian Kronenberg; Bernhard Paulweber; Nicole Aumann; Karlhans Endlich; Mike Pietzner; Uwe Voelker; Rainer Rettig; Vincent Chouraki; Catherine Helmer; Jean-Charles Lambert; Marie Metzger; Benedicte Stengel; Terho Lehtimaki; Leo-Pekka Lyytikainen; Olli Raitakari; Andrew Johnson; Afshin Parsa; Murielle Bochud; Iris M Heid; Wolfram Goessling; Anna Kottgen; W. H. Linda Kao; Caroline S Fox; Carsten A Boeger

doi:10.1038/ki.2014.361

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Genome-wide association study of kidney function decline in individuals of European descent

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Genome-wide association study of kidney function decline in individuals of European descent

Mathias Gorski, Adrienne Tin, Maija Garnaas, Gearoid M McMahon, Audrey Y Chu, Bamidele O Tayo, Cristian Pattaro, Alexander Teumer, Daniel I Chasman, John Chalmers, …

Kidney international, Vol.87(5), pp.1017-1029

05-01-2015

DOI: https://doi.org/10.1038/ki.2014.361

PMID: 25493955

Abstract

Life Sciences & Biomedicine

Science & Technology

Urology & Nephrology

Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.

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Title: Genome-wide association study of kidney function decline in individuals of European descent
Creators: Mathias Gorski - University of Regensburg
Adrienne Tin - Johns Hopkins University
Maija Garnaas - Harvard University
Gearoid M McMahon - Brigham and Women's Hospital
Audrey Y Chu - Harvard University
Bamidele O Tayo - Loyola University Chicago
Cristian Pattaro - Univ Lubeck, European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy
Alexander Teumer - Universität Greifswald
Daniel I Chasman - Harvard University
John Chalmers - The University of Sydney
Pavel Hamet - Université de Montréal
Johanne Tremblay - Université de Montréal
Marc Woodward - The University of Sydney
Thor Aspelund - University of Iceland
Gudny Eiriksdottir - Icelandic Heart Assoc, Res Inst, Kopavogur, Iceland
Vilmundur Gudnason - University of Iceland
Tamara B Harris - National Institutes of Health
Lenore J Launer - National Institutes of Health
Albert V Smith - University of Iceland
Braxton D Mitchell - University of Maryland, Baltimore
Jeffrey R O'Connell - University of Maryland, Baltimore
Alan R Shuldiner - University of Maryland, Baltimore
Josef Coresh - Johns Hopkins University
Man Li - Johns Hopkins University
Paul Freudenberger - Medical University of Graz
Edith Hofer - Medical University of Graz
Helena Schmidt - Medical University of Graz
Reinhold Schmidt - Medical University of Graz
Elizabeth G Holliday - University of Newcastle Australia
Paul Mitchell - The University of Sydney
Jie Jin Wang - The University of Sydney
Ian H de Boer - University of Washington
Guo Li - University of Washington
David S Siscovick - University of Washington
Zoltan Kutalik - SIB Swiss Institute of Bioinformatics
Tanguy Corre - University of Lausanne
Peter Vollenweider - University of Lausanne
Gerard Waeber - University of Lausanne
Jayanta Gupta - University of Pennsylvania
Peter A Kanetsky - University of Pennsylvania
Shih-Jen Hwang - National Institutes of Health
Matthias Olden - University of Regensburg
Qiong Yang - Boston University
Mariza de Andrade - Mayo Clinic
Elizabeth J Atkinson - Mayo Clinic
Sharon L. R Kardia - University of Michigan
Stephen T Turner - Mayo Clinic
Jeanette M Stafford - Wake Forest University
Jingzhong Ding - Wake Forest University
Yongmei Liu - Wake Forest University
Cristina Barlassina - University of Milan
Daniele Cusi - University of Milan
Erika Salvi - University of Milan
Jan A Staessen - Maastricht University
Paul M Ridker - Harvard University
Harald Grallert - Helmholtz Zentrum München
Christa Meisinger - Helmholtz Zentrum München
Martina Mueller-Nurasyid - DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany
Bernhard K Kraemer - Heidelberg Univ, Univ Med Ctr Mannheim, Dept Med 5, Mannheim, Germany
Holly Kramer - Loyola University Chicago
Sylvia E Rosas - Harvard University
Ilja M Nolte - University of Groningen
Brenda W Penninx - Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Psychiat, Amsterdam, Netherlands
Harold Snieder - University of Groningen
M. Fabiola Del Greco - Univ Lubeck, European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy
Andre Franke - Christian-Albrechts-Universität zu Kiel
Ute Noethlings - Univ Hosp Schleswig Holstein, Popgen Biobank, Kiel, Germany
Wolfgang Lieb - Christian-Albrechts-Universität zu Kiel
Stephan J. L Bakker - University of Groningen
Ron T Gansevoort - University of Groningen
Pim van der Harst - University of Groningen
Abbas Dehghan - Erasmus University Rotterdam
Oscar H Franco - Erasmus University Rotterdam
Albert Hofman - Erasmus University Rotterdam
Fernando Rivadeneira - Erasmus University Rotterdam
Sanaz Sedaghat - Erasmus University Rotterdam
Andre G Uitterlinden - Erasmus University Rotterdam
Stefan Coassin - Innsbruck Medical University
Margot Haun - Innsbruck Medical University
Barbara Kollerits - Innsbruck Medical University
Florian Kronenberg - Innsbruck Medical University
Bernhard Paulweber - Paracelsus Private Med Univ Salzburg, Dept Internal Med 1, Salzburg, Austria
Nicole Aumann - Universität Greifswald
Karlhans Endlich - Universität Greifswald
Mike Pietzner - Universität Greifswald
Uwe Voelker - Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany
Rainer Rettig - Universität Greifswald
Vincent Chouraki - Inserm
Catherine Helmer - Université de Bordeaux
Jean-Charles Lambert - Inserm
Marie Metzger - Inserm
Benedicte Stengel - Inserm
Terho Lehtimaki - Fimlab Labs, Dept Clin Chem, Tampere, Finland
Leo-Pekka Lyytikainen - Fimlab Labs, Dept Clin Chem, Tampere, Finland
Olli Raitakari - University of Turku
Andrew Johnson - National Institutes of Health
Afshin Parsa - University of Maryland, Baltimore
Murielle Bochud - University of Lausanne
Iris M Heid - University of Regensburg
Wolfram Goessling - Harvard University
Anna Kottgen - Johns Hopkins University
W. H. Linda Kao - Johns Hopkins University
Caroline S Fox - NHLBI, Framingham Heart Study, Framingham, MA USA
Carsten A Boeger - Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany
Publication Details: Kidney international, Vol.87(5), pp.1017-1029
Publisher: ELSEVIER SCIENCE INC; NEW YORK
Number of pages: 13
Grant note: NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) HHSN268201100005C; HHSN268201100006C; HHSN268201100007C; HHSN268201100008C; HHSN268201100009C; HHSN268201100010C; HHSN268201100011C; HHSN268201100012C; R01HL087641; R01HL59367; R01HL086694 / National Heart, Lung, and Blood Institute HHSN268200625226C / National Institutes of Health KO3598/2- 1 / (Emmy Noether Programme) of the German Research Foundation Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center U01HG004402 / National Human Genome Research Institute M01 RR 16500 / University of Maryland General Clinical Research Center Althingi (the Icelandic Parliament) P20545-P05; P20545-P05 and P13180 / Austrian Science Fond (FWF) UL1RR025005 / component of the National Institutes of Health and NIH Roadmap for Medical Research N01-AG-1-2100; R01 AG18728; R01 HL088119; U01 GM074518-04; U01 HL072515-06; U01 HL084756; K12RR023250; NIH P30 DK072488 / NIH
Identifiers: 99383433120806570
Academic Unit: Department of Health Sciences
Language: English
Resource Type: Journal article

Genome-wide association study of kidney function decline in individuals of European descent

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