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Meta-analysis uncov...
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Gorski, MathiasUniversity Hospital Regensburg,University of Regensburg
(author)
Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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Elsevier,2021
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-430992
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-430992URI
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https://doi.org/10.1016/j.kint.2020.09.030DOI
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https://lup.lub.lu.se/record/bc488d97-e864-4b86-9d56-0c5c664df209URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Jung, Bettina
(author)
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Li, Yong
(author)
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Matias-Garcia, Pamela R.
(author)
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Wuttke, Matthias
(author)
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Coassin, Stefan
(author)
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Thio, Chris H. L.
(author)
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Kleber, Marcus E.
(author)
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Winkler, Thomas W.
(author)
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Wanner, Veronika
(author)
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Chai, Jin-Fang
(author)
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Chu, Audrey Y.
(author)
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Cocca, Massimiliano
(author)
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Feitosa, Mary F.
(author)
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Ghasemi, Sahar
(author)
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Hoppmann, Anselm
(author)
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Horn, Katrin
(author)
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Li, Man
(author)
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Nutile, Teresa
(author)
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Scholz, Markus
(author)
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Sieber, Karsten B.
(author)
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Teumer, Alexander
(author)
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Tin, Adrienne
(author)
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Wang, Judy
(author)
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Tayo, Bamidele O.
(author)
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Ahluwalia, Tarunveer S.
(author)
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Almgren, PeterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Diabetes - kardiovaskulär sjukdom,Kardiovaskulär forskning - hypertoni,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Diabetes - Cardiovascular Disease,Cardiovascular Research - Hypertension(Swepub:lu)endo-pal
(author)
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Bakker, Stephan J. L.
(author)
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Banas, Bernhard
(author)
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Bansal, Nisha
(author)
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Biggs, Mary L.
(author)
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Boerwinkle, Eric
(author)
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Bottinger, Erwin P.
(author)
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Brenner, Hermann
(author)
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Carroll, Robert J.
(author)
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Chalmers, John
(author)
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Chee, Miao-Li
(author)
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Chee, Miao-Ling
(author)
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Cheng, Ching-Yu
(author)
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Coresh, Josef
(author)
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de Borst, Martin H.
(author)
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Degenhardt, Frauke
(author)
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Eckardt, Kai-Uwe
(author)
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Endlich, Karlhans
(author)
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Franke, Andre
(author)
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Freitag-Wolf, Sandra
(author)
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Gampawar, Piyush
(author)
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Gansevoort, Ron T.
(author)
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Ghanbari, Mohsen
(author)
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Gieger, Christian
(author)
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Hamet, Pavel
(author)
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Ho, Kevin
(author)
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Hofer, Edith
(author)
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Holleczek, Bernd
(author)
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Xian Foo, Valencia Hui
(author)
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Hutri-Kähönen, Nina
(author)
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Hwang, Shih-Jen
(author)
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Ikram, M. Arfan
(author)
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Josyula, Navya Shilpa
(author)
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Kähönen, Mika
(author)
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Khor, Chiea-Chuen
(author)
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Koenig, Wolfgang
(author)
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Kramer, Holly
(author)
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Krämer, Bernhard K.
(author)
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Kühnel, Brigitte
(author)
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Lange, Leslie A.
(author)
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Lehtimäki, Terho
(author)
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Lieb, Wolfgang
(author)
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Loos, Ruth J. F.
(author)
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Lukas, Mary Ann
(author)
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Lyytikäinen, Leo-Pekka
(author)
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Meisinger, Christa
(author)
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Meitinger, Thomas
(author)
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Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome
(author)
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Milaneschi, Yuri
(author)
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Mishra, Pashupati P.
(author)
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Mononen, Nina
(author)
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Mychaleckyj, Josyf C.
(author)
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Nadkarni, Girish N.
(author)
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Nauck, Matthias
(author)
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Nikus, Kjell
(author)
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Ning, Boting
(author)
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Nolte, Ilja M.
(author)
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O'Donoghue, Michelle L.
(author)
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Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor
(author)
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Pendergrass, Sarah A.
(author)
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Penninx, Brenda W. J. H.
(author)
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Preuss, Michael H.
(author)
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Psaty, Bruce M.
(author)
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Raffield, Laura M.
(author)
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Raitakari, Olli T.
(author)
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Rettig, Rainer
(author)
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Rheinberger, Myriam
(author)
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Rice, Kenneth M.
(author)
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Rosenkranz, Alexander R.
(author)
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Rossing, Peter
(author)
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Rotter, Jerome I.
(author)
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Sabanayagam, Charumathi
(author)
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Schmidt, Helena
(author)
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Schmidt, Reinhold
(author)
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Schöttker, Ben
(author)
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Schulz, Christina-Alexandra
(author)
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Sedaghat, Sanaz
(author)
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Shaffer, Christian M.
(author)
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Strauch, Konstantin
(author)
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Szymczak, Silke
(author)
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Taylor, Kent D.
(author)
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Tremblay, Johanne
(author)
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Chaker, Layal
(author)
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van der Harst, Pim
(author)
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van der Most, Peter J.
(author)
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Verweij, Niek
(author)
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Völker, Uwe
(author)
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Waldenberger, Melanie
(author)
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Wallentin, Lars,1943-Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)larswall
(author)
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Waterworth, Dawn M.
(author)
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White, Harvey D.
(author)
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Wilson, James G.
(author)
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Wong, Tien-Yin
(author)
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Woodward, Mark
(author)
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Yang, Qiong
(author)
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Yasuda, Masayuki
(author)
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Yerges-Armstrong, Laura M.
(author)
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Zhang, Yan
(author)
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Snieder, Harold
(author)
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Wanner, Christoph
(author)
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Böger, Carsten A.
(author)
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Köttgen, Anna
(author)
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Kronenberg, Florian
(author)
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Pattaro, Cristian
(author)
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Heid, Iris M.University of Regensburg
(author)
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University Hospital RegensburgUniversity of Regensburg
(creator_code:org_t)
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Lifelines Cohort Study
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In:Kidney International: Elsevier99:4, s. 926-9390085-25381523-1755
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Gorski, Mathias
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