@article {8624,
	title = {Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline.},
	journal = {Kidney Int},
	year = {2020},
	month = {2020 Oct 30},
	abstract = {<p>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/1.73m/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25\% or more and eGFRcrea under 60 mL/min/1.73m at follow-up among those with eGFRcrea 60 mL/min/1.73m 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.</p>},
	issn = {1523-1755},
	doi = {10.1016/j.kint.2020.09.030},
	author = {Gorski, Mathias and Jung, Bettina and Li, Yong and Matias-Garcia, Pamela R and Wuttke, Matthias and Coassin, Stefan and Thio, Chris H L and Kleber, Marcus E and Winkler, Thomas W and Wanner, Veronika and Chai, Jin-Fang and Chu, Audrey Y and Cocca, Massimiliano and Feitosa, Mary F and Ghasemi, Sahar and Hoppmann, Anselm and Horn, Katrin and Li, Man and Nutile, Teresa and Scholz, Markus and Sieber, Karsten B and Teumer, Alexander and Tin, Adrienne and Wang, Judy and Tayo, Bamidele O and Ahluwalia, Tarunveer S and Almgren, Peter and Bakker, Stephan J L and Banas, Bernhard and Bansal, Nisha and Biggs, Mary L and Boerwinkle, Eric and Bottinger, Erwin P and Brenner, Hermann and Carroll, Robert J and Chalmers, John and Chee, Miao-Li and Chee, Miao-Ling and Cheng, Ching-Yu and Coresh, Josef and de Borst, Martin H and Degenhardt, Frauke and Eckardt, Kai-Uwe and Endlich, Karlhans and Franke, Andre and Freitag-Wolf, Sandra and Gampawar, Piyush and Gansevoort, Ron T and Ghanbari, Mohsen and Gieger, Christian and Hamet, Pavel and Ho, Kevin and Hofer, Edith and Holleczek, Bernd and Xian Foo, Valencia Hui and Hutri-K{\"a}h{\"o}nen, Nina and Hwang, Shih-Jen and Ikram, M Arfan and Josyula, Navya Shilpa and K{\"a}h{\"o}nen, Mika and Khor, Chiea-Chuen and Koenig, Wolfgang and Kramer, Holly and Kr{\"a}mer, Bernhard K and Kuhnel, Brigitte and Lange, Leslie A and Lehtim{\"a}ki, Terho and Lieb, Wolfgang and Loos, Ruth J F and Lukas, Mary Ann and Lyytik{\"a}inen, Leo-Pekka and Meisinger, Christa and Meitinger, Thomas and Melander, Olle and Milaneschi, Yuri and Mishra, Pashupati P and Mononen, Nina and Mychaleckyj, Josyf C and Nadkarni, Girish N and Nauck, Matthias and Nikus, Kjell and Ning, Boting and Nolte, Ilja M and O{\textquoteright}Donoghue, Michelle L and Orho-Melander, Marju and Pendergrass, Sarah A and Penninx, Brenda W J H and Preuss, Michael H and Psaty, Bruce M and Raffield, Laura M and Raitakari, Olli T and Rettig, Rainer and Rheinberger, Myriam and Rice, Kenneth M and Rosenkranz, Alexander R and Rossing, Peter and Rotter, Jerome I and Sabanayagam, Charumathi and Schmidt, Helena and Schmidt, Reinhold and Sch{\"o}ttker, Ben and Schulz, Christina-Alexandra and Sedaghat, Sanaz and Shaffer, Christian M and Strauch, Konstantin and Szymczak, Silke and Taylor, Kent D and Tremblay, Johanne and Chaker, Layal and van der Harst, Pim and van der Most, Peter J and Verweij, Niek and V{\"o}lker, Uwe and Waldenberger, Melanie and Wallentin, Lars and Waterworth, Dawn M and White, Harvey D and Wilson, James G and Wong, Tien-Yin and Woodward, Mark and Yang, Qiong and Yasuda, Masayuki and Yerges-Armstrong, Laura M and Zhang, Yan and Snieder, Harold and Wanner, Christoph and B{\"o}ger, Carsten A and K{\"o}ttgen, Anna and Kronenberg, Florian and Pattaro, Cristian and Heid, Iris M}
}
