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000180380 0247_ $$2ISSN$$a1523-1755
000180380 0247_ $$2ISSN$$a2157-1716
000180380 0247_ $$2ISSN$$a2157-1724
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000180380 037__ $$aDKFZ-2022-01294
000180380 041__ $$aEnglish
000180380 082__ $$a610
000180380 1001_ $$aGorski, Mathias$$b0
000180380 245__ $$aGenetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies.
000180380 260__ $$aNew York, NY$$bElsevier$$c2022
000180380 3367_ $$2DRIVER$$aarticle
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000180380 500__ $$a2022 Sep;102(3):624-639
000180380 520__ $$aEstimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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000180380 650_7 $$2Other$$aacute kidney injury
000180380 650_7 $$2Other$$achronic kidney disease
000180380 650_7 $$2Other$$adiabetes
000180380 650_7 $$2Other$$agene expression
000180380 7001_ $$aRasheed, Humaira$$b1
000180380 7001_ $$aTeumer, Alexander$$b2
000180380 7001_ $$aThomas, Laurent F$$b3
000180380 7001_ $$aGraham, Sarah E$$b4
000180380 7001_ $$aSveinbjornsson, Gardar$$b5
000180380 7001_ $$aWinkler, Thomas W$$b6
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000180380 7001_ $$aStark, Klaus J$$b8
000180380 7001_ $$aChai, Jin-Fang$$b9
000180380 7001_ $$aTayo, Bamidele O$$b10
000180380 7001_ $$aWuttke, Matthias$$b11
000180380 7001_ $$aLi, Yong$$b12
000180380 7001_ $$aTin, Adrienne$$b13
000180380 7001_ $$aAhluwalia, Tarunveer S$$b14
000180380 7001_ $$aÄrnlöv, Johan$$b15
000180380 7001_ $$aÅsvold, Bjørn Olav$$b16
000180380 7001_ $$aBakker, Stephan J L$$b17
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000180380 7001_ $$aBiggs, Mary L$$b20
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000180380 7001_ $$aBöhnke, Michael$$b22
000180380 7001_ $$aBoerwinkle, Eric$$b23
000180380 7001_ $$aBottinger, Erwin P$$b24
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000180380 7001_ $$aChee, Miao-Li$$b30
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000180380 7001_ $$aCheng, Ching-Yu$$b32
000180380 7001_ $$aChu, Audrey Y$$b33
000180380 7001_ $$aCiullo, Marina$$b34
000180380 7001_ $$aCocca, Massimiliano$$b35
000180380 7001_ $$aCook, James P$$b36
000180380 7001_ $$aCoresh, Josef$$b37
000180380 7001_ $$aCusi, Daniele$$b38
000180380 7001_ $$ade Borst, Martin H$$b39
000180380 7001_ $$aDegenhardt, Frauke$$b40
000180380 7001_ $$aEckardt, Kai-Uwe$$b41
000180380 7001_ $$aEndlich, Karlhans$$b42
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000180380 7001_ $$aGansevoort, Ron T$$b49
000180380 7001_ $$aGhanbari, Mohsen$$b50
000180380 7001_ $$aGhasemi, Sahar$$b51
000180380 7001_ $$aGiedraitis, Vilmantas$$b52
000180380 7001_ $$aGieger, Christian$$b53
000180380 7001_ $$aGudbjartsson, Daniel F$$b54
000180380 7001_ $$aHallan, Stein$$b55
000180380 7001_ $$aHamet, Pavel$$b56
000180380 7001_ $$aHishida, Asahi$$b57
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000180380 7001_ $$aHoppmann, Anselm$$b62
000180380 7001_ $$aHorn, Katrin$$b63
000180380 7001_ $$aHutri-Kähönen, Nina$$b64
000180380 7001_ $$aHveem, Kristian$$b65
000180380 7001_ $$aHwang, Shih-Jen$$b66
000180380 7001_ $$aIkram, M Arfan$$b67
000180380 7001_ $$aJosyula, Navya Shilpa$$b68
000180380 7001_ $$aJung, Bettina$$b69
000180380 7001_ $$aKähönen, Mika$$b70
000180380 7001_ $$aKarabegović, Irma$$b71
000180380 7001_ $$aKhor, Chiea-Chuen$$b72
000180380 7001_ $$aKoenig, Wolfgang$$b73
000180380 7001_ $$aKramer, Holly$$b74
000180380 7001_ $$aKrämer, Bernhard K$$b75
000180380 7001_ $$aKühnel, Brigitte$$b76
000180380 7001_ $$aKuusisto, Johanna$$b77
000180380 7001_ $$aLaakso, Markku$$b78
000180380 7001_ $$aLange, Leslie A$$b79
000180380 7001_ $$aLehtimäki, Terho$$b80
000180380 7001_ $$aLi, Man$$b81
000180380 7001_ $$aLieb, Wolfgang$$b82
000180380 7001_ $$astudy, Lifelines cohort$$b83$$eCollaboration Author
000180380 7001_ $$aLind, Lars$$b84
000180380 7001_ $$aLindgren, Cecilia M$$b85
000180380 7001_ $$aLoos, Ruth J F$$b86
000180380 7001_ $$aLukas, Mary Ann$$b87
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000180380 7001_ $$aMatias-Garcia, Pamela R$$b90
000180380 7001_ $$aMeisinger, Christa$$b91
000180380 7001_ $$aMeitinger, Thomas$$b92
000180380 7001_ $$aMelander, Olle$$b93
000180380 7001_ $$aMilaneschi, Yuri$$b94
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000180380 7001_ $$aMononen, Nina$$b96
000180380 7001_ $$aMorris, Andrew P$$b97
000180380 7001_ $$aMychaleckyj, Josyf C$$b98
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000180380 7001_ $$aNaito, Mariko$$b100
000180380 7001_ $$aNakatochi, Masahiro$$b101
000180380 7001_ $$aNalls, Mike A$$b102
000180380 7001_ $$aNauck, Matthias$$b103
000180380 7001_ $$aNikus, Kjell$$b104
000180380 7001_ $$aNing, Boting$$b105
000180380 7001_ $$aNolte, Ilja M$$b106
000180380 7001_ $$aNutile, Teresa$$b107
000180380 7001_ $$aO'Donoghue, Michelle L$$b108
000180380 7001_ $$aO'Connell, Jeffrey$$b109
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000180380 7001_ $$aRaffield, Laura M$$b118
000180380 7001_ $$aRaitakari, Olli T$$b119
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