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000164261 0247_ $$2ISSN$$a2157-1724
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000164261 1001_ $$aGorski, Mathias$$b0
000164261 245__ $$aMeta-analysis uncovers genome-wide significant variants for rapid kidney function decline.
000164261 260__ $$aNew York, NY$$bElsevier$$c2021
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000164261 500__ $$a2021 Apr;99(4):926-939
000164261 520__ $$aRapid 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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000164261 7001_ $$aLi, Yong$$b2
000164261 7001_ $$aMatias-Garcia, Pamela R$$b3
000164261 7001_ $$aWuttke, Matthias$$b4
000164261 7001_ $$aCoassin, Stefan$$b5
000164261 7001_ $$aThio, Chris H L$$b6
000164261 7001_ $$aKleber, Marcus E$$b7
000164261 7001_ $$aWinkler, Thomas W$$b8
000164261 7001_ $$aWanner, Veronika$$b9
000164261 7001_ $$aChai, Jin-Fang$$b10
000164261 7001_ $$aChu, Audrey Y$$b11
000164261 7001_ $$aCocca, Massimiliano$$b12
000164261 7001_ $$aFeitosa, Mary F$$b13
000164261 7001_ $$aGhasemi, Sahar$$b14
000164261 7001_ $$aHoppmann, Anselm$$b15
000164261 7001_ $$aHorn, Katrin$$b16
000164261 7001_ $$aLi, Man$$b17
000164261 7001_ $$aNutile, Teresa$$b18
000164261 7001_ $$aScholz, Markus$$b19
000164261 7001_ $$aSieber, Karsten B$$b20
000164261 7001_ $$aTeumer, Alexander$$b21
000164261 7001_ $$aTin, Adrienne$$b22
000164261 7001_ $$aWang, Judy$$b23
000164261 7001_ $$aTayo, Bamidele O$$b24
000164261 7001_ $$aAhluwalia, Tarunveer S$$b25
000164261 7001_ $$aAlmgren, Peter$$b26
000164261 7001_ $$aBakker, Stephan J L$$b27
000164261 7001_ $$aBanas, Bernhard$$b28
000164261 7001_ $$aBansal, Nisha$$b29
000164261 7001_ $$aBiggs, Mary L$$b30
000164261 7001_ $$aBoerwinkle, Eric$$b31
000164261 7001_ $$aBottinger, Erwin P$$b32
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000164261 7001_ $$aCarroll, Robert J$$b34
000164261 7001_ $$aChalmers, John$$b35
000164261 7001_ $$aChee, Miao-Li$$b36
000164261 7001_ $$aChee, Miao-Ling$$b37
000164261 7001_ $$aCheng, Ching-Yu$$b38
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000164261 7001_ $$aGansevoort, Ron T$$b47
000164261 7001_ $$aGhanbari, Mohsen$$b48
000164261 7001_ $$aGieger, Christian$$b49
000164261 7001_ $$aHamet, Pavel$$b50
000164261 7001_ $$aHo, Kevin$$b51
000164261 7001_ $$aHofer, Edith$$b52
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000164261 7001_ $$aXian Foo, Valencia Hui$$b54
000164261 7001_ $$aHutri-Kähönen, Nina$$b55
000164261 7001_ $$aHwang, Shih-Jen$$b56
000164261 7001_ $$aIkram, M Arfan$$b57
000164261 7001_ $$aJosyula, Navya Shilpa$$b58
000164261 7001_ $$aKähönen, Mika$$b59
000164261 7001_ $$aKhor, Chiea-Chuen$$b60
000164261 7001_ $$aKoenig, Wolfgang$$b61
000164261 7001_ $$aKramer, Holly$$b62
000164261 7001_ $$aKrämer, Bernhard K$$b63
000164261 7001_ $$aKühnel, Brigitte$$b64
000164261 7001_ $$aLange, Leslie A$$b65
000164261 7001_ $$aLehtimäki, Terho$$b66
000164261 7001_ $$aLieb, Wolfgang$$b67
000164261 7001_ $$astudy, Lifelines cohort$$b68$$eCollaboration Author
000164261 7001_ $$aCenter, Regeneron Genetics$$b69$$eCollaboration Author
000164261 7001_ $$aLoos, Ruth J F$$b70
000164261 7001_ $$aLukas, Mary Ann$$b71
000164261 7001_ $$aLyytikäinen, Leo-Pekka$$b72
000164261 7001_ $$aMeisinger, Christa$$b73
000164261 7001_ $$aMeitinger, Thomas$$b74
000164261 7001_ $$aMelander, Olle$$b75
000164261 7001_ $$aMilaneschi, Yuri$$b76
000164261 7001_ $$aMishra, Pashupati P$$b77
000164261 7001_ $$aMononen, Nina$$b78
000164261 7001_ $$aMychaleckyj, Josyf C$$b79
000164261 7001_ $$aNadkarni, Girish N$$b80
000164261 7001_ $$aNauck, Matthias$$b81
000164261 7001_ $$aNikus, Kjell$$b82
000164261 7001_ $$aNing, Boting$$b83
000164261 7001_ $$aNolte, Ilja M$$b84
000164261 7001_ $$aO'Donoghue, Michelle L$$b85
000164261 7001_ $$aOrho-Melander, Marju$$b86
000164261 7001_ $$aPendergrass, Sarah A$$b87
000164261 7001_ $$aPenninx, Brenda W J H$$b88
000164261 7001_ $$aPreuss, Michael H$$b89
000164261 7001_ $$aPsaty, Bruce M$$b90
000164261 7001_ $$aRaffield, Laura M$$b91
000164261 7001_ $$aRaitakari, Olli T$$b92
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000164261 7001_ $$aSabanayagam, Charumathi$$b99
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