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Gorski, M.* ; Jung, B.* ; Li, Y.* ; Matias-Garcia, P.R. ; Wuttke, M.* ; Coassin, S.* ; Thio, C.H.L.* ; Kleber, M.E.* ; Winkler, T.W.* ; Wanner, V.* ; Chai, J.F.* ; Chu, A.Y.* ; Cocca, M.* ; Feitosa, M.F.* ; Ghasemi, S.* ; Hoppmann, A.* ; Horn, K.* ; Li, M.* ; Nutile, T.* ; Scholz, M.* ; Sieber, K.B.* ; Teumer, A.* ; Tin, A.* ; Wang, J.* ; Tayo, B.O.* ; Ahluwalia, T.S.* ; Almgren, P.* ; Bakker, S.J.L.* ; Banas, B.* ; Bansal, N.* ; Biggs, M.L.* ; Boerwinkle, E.* ; Bottinger, E.P.* ; Brenner, H.* ; Carroll, R.J.* ; Chalmers, J.* ; Chee, M.L.* ; Cheng, C.Y.* ; Coresh, J.* ; de Borst, M.H.* ; Degenhardt, F.* ; Eckardt, K.U.* ; Endlich, K.* ; Franke, A.* ; Freitag-Wolf, S.* ; Gampawar, P.* ; Gansevoort, R.T.* ; Ghanbari, M.* ; Gieger, C. ; Hamet, P.* ; Ho, K.* ; Hofer, E.* ; Holleczek, B.* ; Xian Foo, V.H.* ; Hutri-Kähönen, N.* ; Hwang, S.J.* ; Ikram, M.A.* ; Josyula, N.S.* ; Kähönen, M.* ; Khor, C.C.* ; Koenig, W.* ; Kramer, H.* ; Krämer, B.K.* ; Kühnel, B. ; Lange, L.A.* ; Lehtimäki, T.* ; Lieb, W.* ; Loos, R.J.F.* ; Lukas, M.A.* ; Lyytikäinen, L.P.* ; Meisinger, C. ; Meitinger, T. ; Melander, O.* ; Milaneschi, Y.* ; Mishra, P.P.* ; Mononen, N.* ; Mychaleckyj, J.C.* ; Nadkarni, G.N.* ; Nauck, M.* ; Nikus, K.* ; Ning, B.* ; Nolte, I.M.* ; O'Donoghue, M.L.* ; Orho-Melander, M.* ; Pendergrass, S.A.* ; Penninx, B.W.J.H.* ; Preuss, M.H.* ; Psaty, B.M.* ; Raffield, L.M.* ; Raitakari, O.T.* ; Rettig, R.* ; Rheinberger, M.* ; Rice, K.M.* ; Rosenkranz, A.R.* ; Rossing, P.* ; Rotter, J.I.* ; Sabanayagam, C.* ; Schmidt, H.* ; Schmidt, R.* ; Schöttker, B.* ; Schulz, C.A.* ; Sedaghat, S.* ; Shaffer, C.M.* ; Strauch, K. ; Szymczak, S.* ; Taylor, K.D.* ; Tremblay, J.* ; Chaker, L.* ; van der Harst, P.* ; van der Most, P.J.* ; Verweij, N.* ; Völker, U.* ; Waldenberger, M. ; Wallentin, L.* ; Waterworth, D.M.* ; White, H.D.* ; Wilson, J.G.* ; Wong, T.Y.* ; Woodward, M.* ; Yang, Q.* ; Yasuda, M.* ; Yerges-Armstrong, L.M.* ; Zhang, Y.* ; Snieder, H.* ; Wanner, C.* ; Böger, C.A.* ; Köttgen, A.* ; Kronenberg, F.* ; Pattaro, C.* ; Heid, I.M.*

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

Kidney Int. 99, 926-939 (2021)
Publ. Version/Full Text Postprint Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genome-wide Association Study ; Acute Kidney Injury ; End-stage Kidney Disease ; Rapid Egfrcrea Decline
ISSN (print) / ISBN 0085-2538
e-ISSN 1523-1755
Journal Kidney International
Quellenangaben Volume: 99, Issue: 4, Pages: 926-939 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Independent Research Group Clinical Epidemiology (KEPI)
Institute of Human Genetics (IHG)
Institute of Genetic Epidemiology (IGE)
Grants CIHR
Medical Research Council
NCATS NIH HHS
NCI NIH HHS
NCRR NIH HHS
NHGRI NIH HHS
NIA NIH HHS
NICHD NIH HHS
NIDDK NIH HHS
NIGMS NIH HHS
NIMHD NIH HHS
NIMH NIH HHS
NHLBI NIH HHS
NINDS NIH HHS