%0 Journal Article %1 GORSKI2021926 %A Gorski, Mathias %A Jung, Bettina %A Li, Yong %A Matias-Garcia, Pamela R. %A Wuttke, Matthias %A Coassin, Stefan %A Thio, Chris H.L. %A Kleber, Marcus E. %A Winkler, Thomas W. %A Wanner, Veronika %A Chai, Jin-Fang %A Chu, Audrey Y. %A Cocca, Massimiliano %A Feitosa, Mary F. %A Ghasemi, Sahar %A Hoppmann, Anselm %A Horn, Katrin %A Li, Man %A Nutile, Teresa %A Scholz, Markus %A Sieber, Karsten B. %A Teumer, Alexander %A Tin, Adrienne %A Wang, Judy %A Tayo, Bamidele O. %A Ahluwalia, Tarunveer S. %A Almgren, Peter %A Bakker, Stephan J.L. %A Banas, Bernhard %A Bansal, Nisha %A Biggs, Mary L. %A Boerwinkle, Eric %A Bottinger, Erwin P. %A Brenner, Hermann %A Carroll, Robert J. %A Chalmers, John %A Chee, Miao-Li %A Chee, Miao-Ling %A Cheng, Ching-Yu %A Coresh, Josef %A de Borst, Martin H. %A Degenhardt, Frauke %A Eckardt, Kai-Uwe %A Endlich, Karlhans %A Franke, Andre %A Freitag-Wolf, Sandra %A Gampawar, Piyush %A Gansevoort, Ron T. %A Ghanbari, Mohsen %A Gieger, Christian %A Hamet, Pavel %A Ho, Kevin %A Hofer, Edith %A Holleczek, Bernd %A Xian Foo, Valencia Hui %A Hutri-Kähönen, Nina %A Hwang, Shih-Jen %A Ikram, M. Arfan %A Josyula, Navya Shilpa %A Kähönen, Mika %A Khor, Chiea-Chuen %A Koenig, Wolfgang %A Kramer, Holly %A Krämer, Bernhard K. %A Kühnel, Brigitte %A Lange, Leslie A. %A Lehtimäki, Terho %A Lieb, Wolfgang %A Alizadeh, Behrooz Z. %A Boezen, H. Marike %A Franke, Lude %A van der Harst, Pim %A Navis, Gerjan %A Rots, Marianne %A Snieder, Harold %A Swertz, Morris %A Wolffenbuttel, Bruce H.R. %A Wijmenga, Cisca %A Abecasis, Goncalo %A Baras, Aris %A Cantor, Michael %A Coppola, Giovanni %A Economides, Aris %A Lotta, Luca A. %A Overton, John D. %A Reid, Jeffrey G. %A Shuldiner, Alan %A Beechert, Christina %A Forsythe, Caitlin %A Fuller, Erin D. %A Gu, Zhenhua %A Lattari, Michael %A Lopez, Alexander %A Overton, John D. %A Schleicher, Thomas D. %A Padilla, Maria Sotiropoulos %A Toledo, Karina %A Widom, Louis %A Wolf, Sarah E. %A Pradhan, Manasi %A Manoochehri, Kia %A Ulloa, Ricardo H. %A Bai, Xiaodong %A Balasubramanian, Suganthi %A Barnard, Leland %A Blumenfeld, Andrew %A Eom, Gisu %A Habegger, Lukas %A Hawes, Alicia %A Khalid, Shareef %A Reid, Jeffrey G. %A Maxwell, Evan K. %A Salerno, William %A Staples, Jeffrey C. %A Jones, Marcus B. %A Mitnaul, Lyndon J. %A Loos, Ruth J.F. %A Lukas, Mary Ann %A Lyytikäinen, Leo-Pekka %A Meisinger, Christa %A Meitinger, Thomas %A Melander, Olle %A Milaneschi, Yuri %A Mishra, Pashupati P. %A Mononen, Nina %A Mychaleckyj, Josyf C. %A Nadkarni, Girish N. %A Nauck, Matthias %A Nikus, Kjell %A Ning, Boting %A Nolte, Ilja M. %A O’Donoghue, Michelle L. %A Orho-Melander, Marju %A Pendergrass, Sarah A. %A Penninx, Brenda W.J.H. %A Preuss, Michael H. %A Psaty, Bruce M. %A Raffield, Laura M. %A Raitakari, Olli T. %A Rettig, Rainer %A Rheinberger, Myriam %A Rice, Kenneth M. %A Rosenkranz, Alexander R. %A Rossing, Peter %A Rotter, Jerome I. %A Sabanayagam, Charumathi %A Schmidt, Helena %A Schmidt, Reinhold %A Schöttker, Ben %A Schulz, Christina-Alexandra %A Sedaghat, Sanaz %A Shaffer, Christian M. %A Strauch, Konstantin %A Szymczak, Silke %A Taylor, Kent D. %A Tremblay, Johanne %A Chaker, Layal %A van der Harst, Pim %A van der Most, Peter J. %A Verweij, Niek %A Völker, Uwe %A Waldenberger, Melanie %A Wallentin, Lars %A Waterworth, Dawn M. %A White, Harvey D. %A Wilson, James G. %A Wong, Tien-Yin %A Woodward, Mark %A Yang, Qiong %A Yasuda, Masayuki %A Yerges-Armstrong, Laura M. %A Zhang, Yan %A Snieder, Harold %A Wanner, Christoph %A Böger, Carsten A. %A Köttgen, Anna %A Kronenberg, Florian %A Pattaro, Cristian %A Heid, Iris M. %D 2021 %J Kidney International %K acute association decline disease, eGFRcrea end-stage genome-wide injury, kidney rapid study, %N 4 %P 926--939 %R https://doi.org/10.1016/j.kint.2020.09.030 %T Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline %U https://www.sciencedirect.com/science/article/pii/S0085253820312394 %V 99 %X 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.

@article{GORSKI2021926, abstract = {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.}, added-at = {2024-10-02T10:38:17.000+0200}, 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-Kähönen, Nina and Hwang, Shih-Jen and Ikram, M. Arfan and Josyula, Navya Shilpa and Kähönen, Mika and Khor, Chiea-Chuen and Koenig, Wolfgang and Kramer, Holly and Krämer, Bernhard K. and Kühnel, Brigitte and Lange, Leslie A. and Lehtimäki, Terho and Lieb, Wolfgang and Alizadeh, Behrooz Z. and Boezen, H. Marike and Franke, Lude and {van der Harst}, Pim and Navis, Gerjan and Rots, Marianne and Snieder, Harold and Swertz, Morris and Wolffenbuttel, Bruce H.R. and Wijmenga, Cisca and Abecasis, Goncalo and Baras, Aris and Cantor, Michael and Coppola, Giovanni and Economides, Aris and Lotta, Luca A. and Overton, John D. and Reid, Jeffrey G. and Shuldiner, Alan and Beechert, Christina and Forsythe, Caitlin and Fuller, Erin D. and Gu, Zhenhua and Lattari, Michael and Lopez, Alexander and Overton, John D. and Schleicher, Thomas D. and Padilla, Maria Sotiropoulos and Toledo, Karina and Widom, Louis and Wolf, Sarah E. and Pradhan, Manasi and Manoochehri, Kia and Ulloa, Ricardo H. and Bai, Xiaodong and Balasubramanian, Suganthi and Barnard, Leland and Blumenfeld, Andrew and Eom, Gisu and Habegger, Lukas and Hawes, Alicia and Khalid, Shareef and Reid, Jeffrey G. and Maxwell, Evan K. and Salerno, William and Staples, Jeffrey C. and Jones, Marcus B. and Mitnaul, Lyndon J. and Loos, Ruth J.F. and Lukas, Mary Ann and Lyytikäinen, 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’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 Schöttker, 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 Völker, 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 Böger, Carsten A. and Köttgen, Anna and Kronenberg, Florian and Pattaro, Cristian and Heid, Iris M.}, biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/2a1c60e87ae89c6cdbad58f63f481a19e/scadsfct}, doi = {https://doi.org/10.1016/j.kint.2020.09.030}, interhash = {80b6ebc79d4632405b5e31e65632c977}, intrahash = {a1c60e87ae89c6cdbad58f63f481a19e}, issn = {0085-2538}, journal = {Kidney International}, keywords = {acute association decline disease, eGFRcrea end-stage genome-wide injury, kidney rapid study,}, number = 4, pages = {926--939}, timestamp = {2024-10-02T10:38:17.000+0200}, title = {Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline}, url = {https://www.sciencedirect.com/science/article/pii/S0085253820312394}, volume = 99, year = 2021 }