TY  - GEN
A1  - Gorski, Mathias
A1  - Jung, Bettina
A1  - Li, Yong
A1  - Matias-Garcia, Pamela R.
A1  - Wuttke, Matthias
A1  - Coassin, Stefan
A1  - Thio, Chris H. L.
A1  - Kleber, Marcus E.
A1  - Winkler, Thomas W.
A1  - Wanner, Veronika
A1  - Chai, Jin-Fang
A1  - Chu, Audrey Y.
A1  - Cocca, Massimiliano
A1  - Feitosa, Mary F.
A1  - Ghasemi, Sahar
A1  - Hoppmann, Anselm
A1  - Horn, Katrin
A1  - Li, Man
A1  - Nutile, Teresa
A1  - Scholz, Markus
A1  - Sieber, Karsten B.
A1  - Teumer, Alexander
A1  - Tin, Adrienne
A1  - Wang, Judy
A1  - Tayo, Bamidele O.
A1  - Ahluwalia, Tarunveer S.
A1  - Almgren, Peter
A1  - Bakker, Stephan J. L.
A1  - Banas, Bernhard
A1  - Bansal, Nisha
A1  - Biggs, Mary L.
A1  - Boerwinkle, Eric
A1  - Böttinger, Erwin
A1  - Brenner, Hermann
A1  - Carroll, Robert J.
A1  - Chalmers, John
A1  - Chee, Miao-Li
A1  - Chee, Miao-Ling
A1  - Cheng, Ching-Yu
A1  - Coresh, Josef
A1  - de Borst, Martin H.
A1  - Degenhardt, Frauke
A1  - Eckardt, Kai-Uwe
A1  - Endlich, Karlhans
A1  - Franke, Andre
A1  - Freitag-Wolf, Sandra
A1  - Gampawar, Piyush
A1  - Gansevoort, Ron T.
A1  - Ghanbari, Mohsen
A1  - Gieger, Christian
A1  - Hamet, Pavel
A1  - Ho, Kevin
A1  - Hofer, Edith
A1  - Holleczek, Bernd
A1  - Foo, Valencia Hui Xian
A1  - Hutri-Kahonen, Nina
A1  - Hwang, Shih-Jen
A1  - Ikram, M. Arfan
A1  - Josyula, Navya Shilpa
A1  - Kahonen, Mika
A1  - Khor, Chiea-Chuen
A1  - Koenig, Wolfgang
A1  - Kramer, Holly
A1  - Kraemer, Bernhard K.
A1  - Kuehnel, Brigitte
A1  - Lange, Leslie A.
A1  - Lehtimaki, Terho
A1  - Lieb, Wolfgang
A1  - Loos, Ruth J. F.
A1  - Lukas, Mary Ann
A1  - Lyytikainen, Leo-Pekka
A1  - Meisinger, Christa
A1  - Meitinger, Thomas
A1  - Melander, Olle
A1  - Milaneschi, Yuri
A1  - Mishra, Pashupati P.
A1  - Mononen, Nina
A1  - Mychaleckyj, Josyf C.
A1  - Nadkarni, Girish N.
A1  - Nauck, Matthias
A1  - Nikus, Kjell
A1  - Ning, Boting
A1  - Nolte, Ilja M.
A1  - O'Donoghue, Michelle L.
A1  - Orho-Melander, Marju
A1  - Pendergrass, Sarah A.
A1  - Penninx, Brenda W. J. H.
A1  - Preuss, Michael H.
A1  - Psaty, Bruce M.
A1  - Raffield, Laura M.
A1  - Raitakari, Olli T.
A1  - Rettig, Rainer
A1  - Rheinberger, Myriam
A1  - Rice, Kenneth M.
A1  - Rosenkranz, Alexander R.
A1  - Rossing, Peter
A1  - Rotter, Jerome
A1  - Sabanayagam, Charumathi
A1  - Schmidt, Helena
A1  - Schmidt, Reinhold
A1  - Schoettker, Ben
A1  - Schulz, Christina-Alexandra
A1  - Sedaghat, Sanaz
A1  - Shaffer, Christian M.
A1  - Strauch, Konstantin
A1  - Szymczak, Silke
A1  - Taylor, Kent D.
A1  - Tremblay, Johanne
A1  - Chaker, Layal
A1  - van der Harst, Pim
A1  - van der Most, Peter J.
A1  - Verweij, Niek
A1  - Voelker, Uwe
A1  - Waldenberger, Melanie
A1  - Wallentin, Lars
A1  - Waterworth, Dawn M.
A1  - White, Harvey D.
A1  - Wilson, James G.
A1  - Wong, Tien-Yin
A1  - Woodward, Mark
A1  - Yang, Qiong
A1  - Yasuda, Masayuki
A1  - Yerges-Armstrong, Laura M.
A1  - Zhang, Yan
A1  - Snieder, Harold
A1  - Wanner, Christoph
A1  - Boger, Carsten A.
A1  - Kottgen, Anna
A1  - Kronenberg, Florian
A1  - Pattaro, Cristian
A1  - Heid, Iris M.
T1  - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
T2  - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät
N2  - 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(2)/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(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) 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.
T3  - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät - 19 
KW  - acute kidney injury
KW  - end-stage kidney disease
KW  - genome-wide association
KW  - study
KW  - rapid eGFRcrea decline
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-565379
IS  - 19
ER  - 
TY  - JOUR
A1  - Wuttke, Matthias
A1  - Li, Yong
A1  - Li, Man
A1  - Sieber, Karsten B.
A1  - Feitosa, Mary F.
A1  - Gorski, Mathias
A1  - Tin, Adrienne
A1  - Wang, Lihua
A1  - Chu, Audrey Y.
A1  - Hoppmann, Anselm
A1  - Kirsten, Holger
A1  - Giri, Ayush
A1  - Chai, Jin-Fang
A1  - Sveinbjornsson, Gardar
A1  - Tayo, Bamidele O.
A1  - Nutile, Teresa
A1  - Fuchsberger, Christian
A1  - Marten, Jonathan
A1  - Cocca, Massimiliano
A1  - Ghasemi, Sahar
A1  - Xu, Yizhe
A1  - Horn, Katrin
A1  - Noce, Damia
A1  - Van der Most, Peter J.
A1  - Sedaghat, Sanaz
A1  - Yu, Zhi
A1  - Akiyama, Masato
A1  - Afaq, Saima
A1  - Ahluwalia, Tarunveer Singh
A1  - Almgren, Peter
A1  - Amin, Najaf
A1  - Arnlov, Johan
A1  - Bakker, Stephan J. L.
A1  - Bansal, Nisha
A1  - Baptista, Daniela
A1  - Bergmann, Sven
A1  - Biggs, Mary L.
A1  - Biino, Ginevra
A1  - Boehnke, Michael
A1  - Boerwinkle, Eric
A1  - Boissel, Mathilde
A1  - Böttinger, Erwin
A1  - Boutin, Thibaud S.
A1  - Brenner, Hermann
A1  - Brumat, Marco
A1  - Burkhardt, Ralph
A1  - Butterworth, Adam S.
A1  - Campana, Eric
A1  - Campbell, Archie
A1  - Campbell, Harry
A1  - Canouil, Mickael
A1  - Carroll, Robert J.
A1  - Catamo, Eulalia
A1  - Chambers, John C.
A1  - Chee, Miao-Ling
A1  - Chee, Miao-Li
A1  - Chen, Xu
A1  - Cheng, Ching-Yu
A1  - Cheng, Yurong
A1  - Christensen, Kaare
A1  - Cifkova, Renata
A1  - Ciullo, Marina
A1  - Concas, Maria Pina
A1  - Cook, James P.
A1  - Coresh, Josef
A1  - Corre, Tanguy
A1  - Sala, Cinzia Felicita
A1  - Cusi, Daniele
A1  - Danesh, John
A1  - Daw, E. Warwick
A1  - De Borst, Martin H.
A1  - De Grandi, Alessandro
A1  - De Mutsert, Renee
A1  - De Vries, Aiko P. J.
A1  - Degenhardt, Frauke
A1  - Delgado, Graciela
A1  - Demirkan, Ayse
A1  - Di Angelantonio, Emanuele
A1  - Dittrich, Katalin
A1  - Divers, Jasmin
A1  - Dorajoo, Rajkumar
A1  - Eckardt, Kai-Uwe
A1  - Ehret, Georg
A1  - Elliott, Paul
A1  - Endlich, Karlhans
A1  - Evans, Michele K.
A1  - Felix, Janine F.
A1  - Foo, Valencia Hui Xian
A1  - Franco, Oscar H.
A1  - Franke, Andre
A1  - Freedman, Barry I.
A1  - Freitag-Wolf, Sandra
A1  - Friedlander, Yechiel
A1  - Froguel, Philippe
A1  - Gansevoort, Ron T.
A1  - Gao, He
A1  - Gasparini, Paolo
A1  - Gaziano, J. Michael
A1  - Giedraitis, Vilmantas
A1  - Gieger, Christian
A1  - Girotto, Giorgia
A1  - Giulianini, Franco
A1  - Gogele, Martin
A1  - Gordon, Scott D.
A1  - Gudbjartsson, Daniel F.
A1  - Gudnason, Vilmundur
A1  - Haller, Toomas
A1  - Hamet, Pavel
A1  - Harris, Tamara B.
A1  - Hartman, Catharina A.
A1  - Hayward, Caroline
A1  - Hellwege, Jacklyn N.
A1  - Heng, Chew-Kiat
A1  - Hicks, Andrew A.
A1  - Hofer, Edith
A1  - Huang, Wei
A1  - Hutri-Kahonen, Nina
A1  - Hwang, Shih-Jen
A1  - Ikram, M. Arfan
A1  - Indridason, Olafur S.
A1  - Ingelsson, Erik
A1  - Ising, Marcus
A1  - Jaddoe, Vincent W. V.
A1  - Jakobsdottir, Johanna
A1  - Jonas, Jost B.
A1  - Joshi, Peter K.
A1  - Josyula, Navya Shilpa
A1  - Jung, Bettina
A1  - Kahonen, Mika
A1  - Kamatani, Yoichiro
A1  - Kammerer, Candace M.
A1  - Kanai, Masahiro
A1  - Kastarinen, Mika
A1  - Kerr, Shona M.
A1  - Khor, Chiea-Chuen
A1  - Kiess, Wieland
A1  - Kleber, Marcus E.
A1  - Koenig, Wolfgang
A1  - Kooner, Jaspal S.
A1  - Korner, Antje
A1  - Kovacs, Peter
A1  - Kraja, Aldi T.
A1  - Krajcoviechova, Alena
A1  - Kramer, Holly
A1  - Kramer, Bernhard K.
A1  - Kronenberg, Florian
A1  - Kubo, Michiaki
A1  - Kuhnel, Brigitte
A1  - Kuokkanen, Mikko
A1  - Kuusisto, Johanna
A1  - La Bianca, Martina
A1  - Laakso, Markku
A1  - Lange, Leslie A.
A1  - Langefeld, Carl D.
A1  - Lee, Jeannette Jen-Mai
A1  - Lehne, Benjamin
A1  - Lehtimaki, Terho
A1  - Lieb, Wolfgang
A1  - Lim, Su-Chi
A1  - Lind, Lars
A1  - Lindgren, Cecilia M.
A1  - Liu, Jun
A1  - Liu, Jianjun
A1  - Loeffler, Markus
A1  - Loos, Ruth J. F.
A1  - Lucae, Susanne
A1  - Lukas, Mary Ann
A1  - Lyytikainen, Leo-Pekka
A1  - Magi, Reedik
A1  - Magnusson, Patrik K. E.
A1  - Mahajan, Anubha
A1  - Martin, Nicholas G.
A1  - Martins, Jade
A1  - Marz, Winfried
A1  - Mascalzoni, Deborah
A1  - Matsuda, Koichi
A1  - Meisinger, Christa
A1  - Meitinger, Thomas
A1  - Melander, Olle
A1  - Metspalu, Andres
A1  - Mikaelsdottir, Evgenia K.
A1  - Milaneschi, Yuri
A1  - Miliku, Kozeta
A1  - Mishra, Pashupati P.
A1  - Program, V. A. Million Veteran
A1  - Mohlke, Karen L.
A1  - Mononen, Nina
A1  - Montgomery, Grant W.
A1  - Mook-Kanamori, Dennis O.
A1  - Mychaleckyj, Josyf C.
A1  - Nadkarni, Girish N.
A1  - Nalls, Mike A.
A1  - Nauck, Matthias
A1  - Nikus, Kjell
A1  - Ning, Boting
A1  - Nolte, Ilja M.
A1  - Noordam, Raymond
A1  - Olafsson, Isleifur
A1  - Oldehinkel, Albertine J.
A1  - Orho-Melander, Marju
A1  - Ouwehand, Willem H.
A1  - Padmanabhan, Sandosh
A1  - Palmer, Nicholette D.
A1  - Palsson, Runolfur
A1  - Penninx, Brenda W. J. H.
A1  - Perls, Thomas
A1  - Perola, Markus
A1  - Pirastu, Mario
A1  - Pirastu, Nicola
A1  - Pistis, Giorgio
A1  - Podgornaia, Anna I.
A1  - Polasek, Ozren
A1  - Ponte, Belen
A1  - Porteous, David J.
A1  - Poulain, Tanja
A1  - Pramstaller, Peter P.
A1  - Preuss, Michael H.
A1  - Prins, Bram P.
A1  - Province, Michael A.
A1  - Rabelink, Ton J.
A1  - Raffield, Laura M.
A1  - Raitakari, Olli T.
A1  - Reilly, Dermot F.
A1  - Rettig, Rainer
A1  - Rheinberger, Myriam
A1  - Rice, Kenneth M.
A1  - Ridker, Paul M.
A1  - Rivadeneira, Fernando
A1  - Rizzi, Federica
A1  - Roberts, David J.
A1  - Robino, Antonietta
A1  - Rossing, Peter
A1  - Rudan, Igor
A1  - Rueedi, Rico
A1  - Ruggiero, Daniela
A1  - Ryan, Kathleen A.
A1  - Saba, Yasaman
A1  - Sabanayagam, Charumathi
A1  - Salomaa, Veikko
A1  - Salvi, Erika
A1  - Saum, Kai-Uwe
A1  - Schmidt, Helena
A1  - Schmidt, Reinhold
A1  - Ben Schottker, 
A1  - Schulz, Christina-Alexandra
A1  - Schupf, Nicole
A1  - Shaffer, Christian M.
A1  - Shi, Yuan
A1  - Smith, Albert V.
A1  - Smith, Blair H.
A1  - Soranzo, Nicole
A1  - Spracklen, Cassandra N.
A1  - Strauch, Konstantin
A1  - Stringham, Heather M.
A1  - Stumvoll, Michael
A1  - Svensson, Per O.
A1  - Szymczak, Silke
A1  - Tai, E-Shyong
A1  - Tajuddin, Salman M.
A1  - Tan, Nicholas Y. Q.
A1  - Taylor, Kent D.
A1  - Teren, Andrej
A1  - Tham, Yih-Chung
A1  - Thiery, Joachim
A1  - Thio, Chris H. L.
A1  - Thomsen, Hauke
A1  - Thorleifsson, Gudmar
A1  - Toniolo, Daniela
A1  - Tonjes, Anke
A1  - Tremblay, Johanne
A1  - Tzoulaki, Ioanna
A1  - Uitterlinden, Andre G.
A1  - Vaccargiu, Simona
A1  - Van Dam, Rob M.
A1  - Van der Harst, Pim
A1  - Van Duijn, Cornelia M.
A1  - Edward, Digna R. Velez
A1  - Verweij, Niek
A1  - Vogelezang, Suzanne
A1  - Volker, Uwe
A1  - Vollenweider, Peter
A1  - Waeber, Gerard
A1  - Waldenberger, Melanie
A1  - Wallentin, Lars
A1  - Wang, Ya Xing
A1  - Wang, Chaolong
A1  - Waterworth, Dawn M.
A1  - Bin Wei, Wen
A1  - White, Harvey
A1  - Whitfield, John B.
A1  - Wild, Sarah H.
A1  - Wilson, James F.
A1  - Wojczynski, Mary K.
A1  - Wong, Charlene
A1  - Wong, Tien-Yin
A1  - Xu, Liang
A1  - Yang, Qiong
A1  - Yasuda, Masayuki
A1  - Yerges-Armstrong, Laura M.
A1  - Zhang, Weihua
A1  - Zonderman, Alan B.
A1  - Rotter, Jerome I.
A1  - Bochud, Murielle
A1  - Psaty, Bruce M.
A1  - Vitart, Veronique
A1  - Wilson, James G.
A1  - Dehghan, Abbas
A1  - Parsa, Afshin
A1  - Chasman, Daniel I.
A1  - Ho, Kevin
A1  - Morris, Andrew P.
A1  - Devuyst, Olivier
A1  - Akilesh, Shreeram
A1  - Pendergrass, Sarah A.
A1  - Sim, Xueling
A1  - Boger, Carsten A.
A1  - Okada, Yukinori
A1  - Edwards, Todd L.
A1  - Snieder, Harold
A1  - Stefansson, Kari
A1  - Hung, Adriana M.
A1  - Heid, Iris M.
A1  - Scholz, Markus
A1  - Teumer, Alexander
A1  - Kottgen, Anna
A1  - Pattaro, Cristian
T1  - A catalog of genetic loci associated with kidney function from analyses of a million individuals
JF  - Nature genetics
N2  - Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Y1  - 2019
U6  - https://doi.org/10.1038/s41588-019-0407-x
SN  - 1061-4036
SN  - 1546-1718
VL  - 51
IS  - 6
SP  - 957
EP  - +
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Gorski, Mathias
A1  - Jung, Bettina
A1  - Li, Yong
A1  - Matias-Garcia, Pamela R.
A1  - Wuttke, Matthias
A1  - Coassin, Stefan
A1  - Thio, Chris H. L.
A1  - Kleber, Marcus E.
A1  - Winkler, Thomas W.
A1  - Wanner, Veronika
A1  - Chai, Jin-Fang
A1  - Chu, Audrey Y.
A1  - Cocca, Massimiliano
A1  - Feitosa, Mary F.
A1  - Ghasemi, Sahar
A1  - Hoppmann, Anselm
A1  - Horn, Katrin
A1  - Li, Man
A1  - Nutile, Teresa
A1  - Scholz, Markus
A1  - Sieber, Karsten B.
A1  - Teumer, Alexander
A1  - Tin, Adrienne
A1  - Wang, Judy
A1  - Tayo, Bamidele O.
A1  - Ahluwalia, Tarunveer S.
A1  - Almgren, Peter
A1  - Bakker, Stephan J. L.
A1  - Banas, Bernhard
A1  - Bansal, Nisha
A1  - Biggs, Mary L.
A1  - Boerwinkle, Eric
A1  - Böttinger, Erwin
A1  - Brenner, Hermann
A1  - Carroll, Robert J.
A1  - Chalmers, John
A1  - Chee, Miao-Li
A1  - Chee, Miao-Ling
A1  - Cheng, Ching-Yu
A1  - Coresh, Josef
A1  - de Borst, Martin H.
A1  - Degenhardt, Frauke
A1  - Eckardt, Kai-Uwe
A1  - Endlich, Karlhans
A1  - Franke, Andre
A1  - Freitag-Wolf, Sandra
A1  - Gampawar, Piyush
A1  - Gansevoort, Ron T.
A1  - Ghanbari, Mohsen
A1  - Gieger, Christian
A1  - Hamet, Pavel
A1  - Ho, Kevin
A1  - Hofer, Edith
A1  - Holleczek, Bernd
A1  - Foo, Valencia Hui Xian
A1  - Hutri-Kahonen, Nina
A1  - Hwang, Shih-Jen
A1  - Ikram, M. Arfan
A1  - Josyula, Navya Shilpa
A1  - Kahonen, Mika
A1  - Khor, Chiea-Chuen
A1  - Koenig, Wolfgang
A1  - Kramer, Holly
A1  - Kraemer, Bernhard K.
A1  - Kuehnel, Brigitte
A1  - Lange, Leslie A.
A1  - Lehtimaki, Terho
A1  - Lieb, Wolfgang
A1  - Loos, Ruth J. F.
A1  - Lukas, Mary Ann
A1  - Lyytikainen, Leo-Pekka
A1  - Meisinger, Christa
A1  - Meitinger, Thomas
A1  - Melander, Olle
A1  - Milaneschi, Yuri
A1  - Mishra, Pashupati P.
A1  - Mononen, Nina
A1  - Mychaleckyj, Josyf C.
A1  - Nadkarni, Girish N.
A1  - Nauck, Matthias
A1  - Nikus, Kjell
A1  - Ning, Boting
A1  - Nolte, Ilja M.
A1  - O'Donoghue, Michelle L.
A1  - Orho-Melander, Marju
A1  - Pendergrass, Sarah A.
A1  - Penninx, Brenda W. J. H.
A1  - Preuss, Michael H.
A1  - Psaty, Bruce M.
A1  - Raffield, Laura M.
A1  - Raitakari, Olli T.
A1  - Rettig, Rainer
A1  - Rheinberger, Myriam
A1  - Rice, Kenneth M.
A1  - Rosenkranz, Alexander R.
A1  - Rossing, Peter
A1  - Rotter, Jerome
A1  - Sabanayagam, Charumathi
A1  - Schmidt, Helena
A1  - Schmidt, Reinhold
A1  - Schoettker, Ben
A1  - Schulz, Christina-Alexandra
A1  - Sedaghat, Sanaz
A1  - Shaffer, Christian M.
A1  - Strauch, Konstantin
A1  - Szymczak, Silke
A1  - Taylor, Kent D.
A1  - Tremblay, Johanne
A1  - Chaker, Layal
A1  - van der Harst, Pim
A1  - van der Most, Peter J.
A1  - Verweij, Niek
A1  - Voelker, Uwe
A1  - Waldenberger, Melanie
A1  - Wallentin, Lars
A1  - Waterworth, Dawn M.
A1  - White, Harvey D.
A1  - Wilson, James G.
A1  - Wong, Tien-Yin
A1  - Woodward, Mark
A1  - Yang, Qiong
A1  - Yasuda, Masayuki
A1  - Yerges-Armstrong, Laura M.
A1  - Zhang, Yan
A1  - Snieder, Harold
A1  - Wanner, Christoph
A1  - Boger, Carsten A.
A1  - Kottgen, Anna
A1  - Kronenberg, Florian
A1  - Pattaro, Cristian
A1  - Heid, Iris M.
T1  - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
JF  - Kidney international : official journal of the International Society of Nephrology
N2  - 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(2)/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(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) 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.
KW  - acute kidney injury
KW  - end-stage kidney disease
KW  - genome-wide association
KW  - study
KW  - rapid eGFRcrea decline
Y1  - 2020
U6  - https://doi.org/10.1016/j.kint.2020.09.030
SN  - 0085-2538
SN  - 1523-1755
VL  - 99
IS  - 4
SP  - 926
EP  - 939
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Broscheit, Frank
A1  - Bütow, Heike
A1  - Gehrke, Albrecht
A1  - Jahn, Gert
A1  - Jürgens, Christoph
A1  - Kißner, Karl-Heinz
A1  - Klohn, Werner
A1  - Knitschky, Wolfgang
A1  - Mager, Franz-Peter
A1  - Maier, Klaus
A1  - Mühlberger, Wolfgang
A1  - Mülders, Wolfgang
A1  - Rappen-Röhlen, Beate
A1  - Reinhardt, Karl Heinz
A1  - Schmidt, Marianne
A1  - Schmidtke, Kurt-Dietmar
A1  - Volkmann, Hartmut
A1  - Wetzel, Jürgen
T1  - Seydlitz Erdkunde 1 : Ausgabe für Realschulen in Nordrhein-Westfalen
Y1  - 1994
PB  - Schroedel
CY  - Hannover
ER  - 
TY  - BOOK
A1  - Albers, Marion
A1  - Appel, Ivo
A1  - Bauer, Hartmut
A1  - von Bogdandy, Armin
A1  - Britz, Gabriele
A1  - Bumke, Wolfgang
A1  - Fehling, Michael
A1  - Gusy, Christoph
A1  - Hermes, Georg
A1  - Hill, Hermann
A1  - Hoffmann-Riem, Wolfgang
A1  - Holznagel, Bernd
A1  - Köck, Wolfgang
A1  - Ladeur, Karl-Heinz
A1  - Michael, Lothar
A1  - Pitschas, Rainer
A1  - Röhl, Hans Christian
A1  - Rossen-Stahlfeld, Helge
A1  - Sachs, Michael
A1  - Sachsofsky, Ute
A1  - Schmidt-Aßmann, Eberhard
A1  - Schneider, Jens-Peter
A1  - Vesting, Thomas
ED  - Hoffmann-Riem, Wolfgang
ED  - Schmidt-Aßmann, Eberhard
ED  - Voßkuhle, Andreas
T1  - Grundlagen des Verwaltungsrechts : Bd. II Informationsordnung, Verwaltungsverfahren, Handlungsformen
Y1  - 2008
SN  - 978-3-406-54718-8
VL  - 2
PB  - Beck
CY  - München
ER  - 
TY  - JOUR
A1  - Broscheit, Frank
A1  - Bütow, Martin
A1  - Englert, Wolfgang
A1  - Jahn, Gert
A1  - Klohn, Werner
A1  - Knitschky, Wolfgang
A1  - Reinecke, Hans-Joachim
A1  - Müller, Helmut
A1  - Reinhardt, Karl Heinz
A1  - Schmidt, Marianne
A1  - Schmidtke, Kurt-Dietmar
A1  - Schöpflin, F.
A1  - Starke, Rainer
A1  - Vahldiek, B. W.
A1  - Wehrs, Klaus
A1  - Wetzel, Jürgen
T1  - Seydlitz Erdkunde 2
Y1  - 1996
PB  - Schroedel
CY  - Hannover
ER  - 
TY  - JOUR
A1  - Schmidt, Andreas
A1  - Rabsch, Wolfgang
A1  - Broeker, Nina K.
A1  - Barbirz, Stefanie
T1  - Bacteriophage tailspike protein based assay to monitor phase variable glucosylations in Salmonella O-antigens
JF  - BMC microbiology
N2  - Background

Non-typhoid Salmonella Typhimurium (S. Typhimurium) accounts for a high number of registered salmonellosis cases, and O-serotyping is one important tool for monitoring epidemiology and spread of the disease. Moreover, variations in glucosylated O-antigens are related to immunogenicity and spread in the host. However, classical autoagglutination tests combined with the analysis of specific genetic markers cannot always reliably register phase variable glucose modifications expressed on Salmonella O-antigens and additional tools to monitor O-antigen glucosylation phenotypes of S. Typhimurium would be desirable.

Results

We developed a test for the phase variable O-antigen glucosylation state of S. Typhimurium using the tailspike proteins (TSP) of Salmonella phages 9NA and P22. We used this ELISA like tailspike adsorption (ELITA) assay to analyze a library of 44 Salmonella strains. ELITA was successful in discriminating strains that carried glucose 1-6 linked to the galactose of O-polysaccharide backbone (serotype O1) from non-glucosylated strains. This was shown by O-antigen compositional analyses of the respective strains with mass spectrometry and capillary electrophoresis. The ELITA test worked rapidly in a microtiter plate format and was highly O-antigen specific. Moreover, TSP as probes could also detect glucosylated strains in flow cytometry and distinguish multiphasic cultures differing in their glucosylation state.

Conclusions

Tailspike proteins contain large binding sites with precisely defined specificities and are therefore promising tools to be included in serotyping procedures as rapid serotyping agents in addition to antibodies. In this study, 9NA and P22TSP as probes could specifically distinguish glucosylation phenotypes of Salmonella on microtiter plate assays and in flow cytometry. This opens the possibility for flow sorting of cell populations for subsequent genetic analyses or for monitoring phase variations during large scale O-antigen preparations necessary for vaccine production.
KW  - Salmonella Typhimurium
KW  - O-antigen
KW  - Tailspike protein
KW  - Bacteriophage
KW  - Phase variation
KW  - O-serotyping
KW  - Flow cytometry
Y1  - 2016
U6  - https://doi.org/10.1186/s12866-016-0826-0
SN  - 1471-2180
VL  - 16
PB  - BioMed Central
CY  - London
ER  - 
TY  - GEN
A1  - Schmidt, Andreas
A1  - Rabsch, Wolfgang
A1  - Broeker, Nina K.
A1  - Barbirz, Stefanie
T1  - Bacteriophage tailspike protein based assay to monitor phase variable glucosylations in Salmonella O-antigens
N2  - Background

Non-typhoid Salmonella Typhimurium (S. Typhimurium) accounts for a high number of registered salmonellosis cases, and O-serotyping is one important tool for monitoring epidemiology and spread of the disease. Moreover, variations in glucosylated O-antigens are related to immunogenicity and spread in the host. However, classical autoagglutination tests combined with the analysis of specific genetic markers cannot always reliably register phase variable glucose modifications expressed on Salmonella O-antigens and additional tools to monitor O-antigen glucosylation phenotypes of S. Typhimurium would be desirable.

Results

We developed a test for the phase variable O-antigen glucosylation state of S. Typhimurium using the tailspike proteins (TSP) of Salmonella phages 9NA and P22. We used this ELISA like tailspike adsorption (ELITA) assay to analyze a library of 44 Salmonella strains. ELITA was successful in discriminating strains that carried glucose 1-6 linked to the galactose of O-polysaccharide backbone (serotype O1) from non-glucosylated strains. This was shown by O-antigen compositional analyses of the respective strains with mass spectrometry and capillary electrophoresis. The ELITA test worked rapidly in a microtiter plate format and was highly O-antigen specific. Moreover, TSP as probes could also detect glucosylated strains in flow cytometry and distinguish multiphasic cultures differing in their glucosylation state.

Conclusions

Tailspike proteins contain large binding sites with precisely defined specificities and are therefore promising tools to be included in serotyping procedures as rapid serotyping agents in addition to antibodies. In this study, 9NA and P22TSP as probes could specifically distinguish glucosylation phenotypes of Salmonella on microtiter plate assays and in flow cytometry. This opens the possibility for flow sorting of cell populations for subsequent genetic analyses or for monitoring phase variations during large scale O-antigen preparations necessary for vaccine production.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 313 
KW  - Bacteriophage
KW  - Flow cytometry
KW  - O-antigen
KW  - O-serotyping
KW  - Phase variation
KW  - Salmonella Typhimurium
KW  - Tailspike protein
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-103769
ER  - 
TY  - JOUR
A1  - Lay, Barbara
A1  - Ihle, Wolfgang
A1  - Esser, Günter
A1  - Schmidt, Martin H.
T1  - Juvenile-episodic, continued or adult-onset delinquency? Risk conditions analysed in a cohort of children followed up to the age of 25 years
Y1  - 2005
ER  - 
TY  - JOUR
A1  - Ihle, Wolfgang
A1  - Esser, Günter
A1  - Schmidt, M. H.
T1  - Aggressiv-dissoziale Störungen und rechtsextreme Einstellungen : Prävalenz, Geschlechtsunterschiede, Verlauf und Risikofaktoren
Y1  - 2005
ER  -