Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Data Sharing Under the General Data Protection Regulation: Time to Harmonize Law and Research Ethics?

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Finerenone and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  • 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
  • Peter Rossing
  • LifeLines Cohort study
View graph of relations

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.

Original languageEnglish
JournalKidney International
Volume99
Issue number4
Pages (from-to)4, P926-939
ISSN0085-2538
DOIs
Publication statusPublished - 1 Apr 2021

ID: 61252057