| Title: | Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline |
| Journal: | Kidney International |
| Published: | 31 Oct 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33137338/ |
| DOI: | https://doi.org/10.1016/j.kint.2020.09.030 |
| URL: | http://www.kidney-international.org/article/S0085253820312394/pdf |
| Citations: | 57 (35 in last 2 years) as of 8 Aug 2024 |
Publication 5388
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Abstract
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.</p>
179 Authors
- Mathias Gorski
- Bettina Jung
- Yong Li
- Pamela R. Matias-Garcia
- Matthias Wuttke
- Stefan Coassin
- Chris H.L. Thio
- Marcus E. Kleber
- Thomas W. Winkler
- Veronika Wanner
- Jin-Fang Chai
- Audrey Y. Chu
- Massimiliano Cocca
- Mary F. Feitosa
- Sahar Ghasemi
- Anselm Hoppmann
- Katrin Horn
- Man Li
- Teresa Nutile
- Markus Scholz
- Karsten B. Sieber
- Alexander Teumer
- Adrienne Tin
- Judy Wang
- Bamidele O. Tayo
- Tarunveer S. Ahluwalia
- Peter Almgren
- Stephan J.L. Bakker
- Bernhard Banas
- Nisha Bansal
- Mary L. Biggs
- Eric Boerwinkle
- Erwin P. Bottinger
- Hermann Brenner
- Robert J. Carroll
- John Chalmers
- Miao-Li Chee
- Miao-Ling Chee
- Ching-Yu Cheng
- Josef Coresh
- Martin H. de Borst
- Frauke Degenhardt
- Kai-Uwe Eckardt
- Karlhans Endlich
- Andre Franke
- Sandra Freitag-Wolf
- Piyush Gampawar
- Ron T. Gansevoort
- Mohsen Ghanbari
- Christian Gieger
- Pavel Hamet
- Kevin Ho
- Edith Hofer
- Bernd Holleczek
- Valencia Hui Xian Foo
- Nina Hutri-Kähönen
- Shih-Jen Hwang
- M. Arfan Ikram
- Navya Shilpa Josyula
- Mika Kähönen
- Chiea-Chuen Khor
- Wolfgang Koenig
- Holly Kramer
- Bernhard K. Krämer
- Brigitte Kühnel
- Leslie A. Lange
- Terho Lehtimäki
- Wolfgang Lieb
- Ruth J.F. Loos
- Mary Ann Lukas
- Leo-Pekka Lyytikäinen
- Christa Meisinger
- Thomas Meitinger
- Olle Melander
- Yuri Milaneschi
- Pashupati P. Mishra
- Nina Mononen
- Josyf C. Mychaleckyj
- Girish N. Nadkarni
- Matthias Nauck
- Kjell Nikus
- Boting Ning
- Ilja M. Nolte
- Michelle L. O'Donoghue
- Marju Orho-Melander
- Sarah A. Pendergrass
- Brenda W.J.H. Penninx
- Michael H. Preuss
- Bruce M. Psaty
- Laura M. Raffield
- Olli T. Raitakari
- Rainer Rettig
- Myriam Rheinberger
- Kenneth M. Rice
- Alexander R. Rosenkranz
- Peter Rossing
- Jerome I. Rotter
- Charumathi Sabanayagam
- Helena Schmidt
- Reinhold Schmidt
- Ben Schöttker
- Christina-Alexandra Schulz
- Sanaz Sedaghat
- Christian M. Shaffer
- Konstantin Strauch
- Silke Szymczak
- Kent D. Taylor
- Johanne Tremblay
- Layal Chaker
- Pim van der Harst
- Peter J. van der Most
- Niek Verweij
- Uwe Völker
- Melanie Waldenberger
- Lars Wallentin
- Dawn M. Waterworth
- Harvey D. White
- James G. Wilson
- Tien-Yin Wong
- Mark Woodward
- Qiong Yang
- Masayuki Yasuda
- Laura M. Yerges-Armstrong
- Yan Zhang
- Harold Snieder
- Christoph Wanner
- Carsten A. Böger
- Anna Köttgen
- Florian Kronenberg
- Cristian Pattaro
- Iris M. Heid
- Behrooz Z. Alizadeh
- H. Marike Boezen
- Lude Franke
- Pim van der Harst
- Gerjan Navis
- Marianne Rots
- Harold Snieder
- Morris Swertz
- Bruce H.R. Wolffenbuttel
- Cisca Wijmenga
- Goncalo Abecasis
- Aris Baras
- Michael Cantor
- Giovanni Coppola
- Aris Economides
- Luca A. Lotta
- John D. Overton
- Jeffrey G. Reid
- Alan Shuldiner
- Christina Beechert
- Caitlin Forsythe
- Erin D. Fuller
- Zhenhua Gu
- Michael Lattari
- Alexander Lopez
- John D. Overton
- Thomas D. Schleicher
- Maria Sotiropoulos Padilla
- Karina Toledo
- Louis Widom
- Sarah E. Wolf
- Manasi Pradhan
- Kia Manoochehri
- Ricardo H. Ulloa
- Xiaodong Bai
- Suganthi Balasubramanian
- Leland Barnard
- Andrew Blumenfeld
- Gisu Eom
- Lukas Habegger
- Alicia Hawes
- Shareef Khalid
- Jeffrey G. Reid
- Evan K. Maxwell
- William Salerno
- Jeffrey C. Staples
- Marcus B. Jones
- Lyndon J. Mitnaul
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