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  - 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  - 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  - Radchuk, Viktoriia
A1  - Reed, Thomas
A1  - Teplitsky, Celine
A1  - van de Pol, Martijn
A1  - Charmantier, Anne
A1  - Hassall, Christopher
A1  - Adamik, Peter
A1  - Adriaensen, Frank
A1  - Ahola, Markus P.
A1  - Arcese, Peter
A1  - Miguel Aviles, Jesus
A1  - Balbontin, Javier
A1  - Berg, Karl S.
A1  - Borras, Antoni
A1  - Burthe, Sarah
A1  - Clobert, Jean
A1  - Dehnhard, Nina
A1  - de Lope, Florentino
A1  - Dhondt, Andre A.
A1  - Dingemanse, Niels J.
A1  - Doi, Hideyuki
A1  - Eeva, Tapio
A1  - Fickel, Jörns
A1  - Filella, Iolanda
A1  - Fossoy, Frode
A1  - Goodenough, Anne E.
A1  - Hall, Stephen J. G.
A1  - Hansson, Bengt
A1  - Harris, Michael
A1  - Hasselquist, Dennis
A1  - Hickler, Thomas
A1  - Jasmin Radha, Jasmin
A1  - Kharouba, Heather
A1  - Gabriel Martinez, Juan
A1  - Mihoub, Jean-Baptiste
A1  - Mills, James A.
A1  - Molina-Morales, Mercedes
A1  - Moksnes, Arne
A1  - Ozgul, Arpat
A1  - Parejo, Deseada
A1  - Pilard, Philippe
A1  - Poisbleau, Maud
A1  - Rousset, Francois
A1  - Rödel, Mark-Oliver
A1  - Scott, David
A1  - Carlos Senar, Juan
A1  - Stefanescu, Constanti
A1  - Stokke, Bard G.
A1  - Kusano, Tamotsu
A1  - Tarka, Maja
A1  - Tarwater, Corey E.
A1  - Thonicke, Kirsten
A1  - Thorley, Jack
A1  - Wilting, Andreas
A1  - Tryjanowski, Piotr
A1  - Merila, Juha
A1  - Sheldon, Ben C.
A1  - Moller, Anders Pape
A1  - Matthysen, Erik
A1  - Janzen, Fredric
A1  - Dobson, F. Stephen
A1  - Visser, Marcel E.
A1  - Beissinger, Steven R.
A1  - Courtiol, Alexandre
A1  - Kramer-Schadt, Stephanie
T1  - Adaptive responses of animals to climate change are most likely insufficient
JF  - Nature Communications
N2  - Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
Y1  - 2019
U6  - https://doi.org/10.1038/s41467-019-10924-4
SN  - 2041-1723
VL  - 10
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Wilting, A.
A1  - Patel, R.
A1  - Pfestorf, Hans
A1  - Kern, C.
A1  - Sultan, K.
A1  - Ario, A.
A1  - Penaloza, F.
A1  - Kramer-Schadt, S.
A1  - Radchuk, Viktoriia
A1  - Foerster, D. W.
A1  - Fickel, Jörns
T1  - Evolutionary history and conservation significance of the Javan leopard Panthera pardus melas
JF  - Journal of zoology : proceedings of the Zoological Society of London
N2  - The leopard Panthera pardus is widely distributed across Africa and Asia; however, there is a gap in its natural distribution in Southeast Asia, where it occurs on the mainland and on Java but not on the interjacent island of Sumatra. Several scenarios have been proposed to explain this distribution gap. Here, we complemented an existing dataset of 68 leopard mtDNA sequences from Africa and Asia with mtDNA sequences (NADH5+ ctrl, 724bp) from 19 Javan leopards, and hindcasted leopard distribution to the Pleistocene to gain further insights into the evolutionary history of the Javan leopard. Our data confirmed that Javan leopards are evolutionarily distinct from other Asian leopards, and that they have been present on Java since the Middle Pleistocene. Species distribution projections suggest that Java was likely colonized via a Malaya-Java land bridge that by-passed Sumatra, as suitable conditions for leopards during Pleistocene glacial periods were restricted to northern and western Sumatra. As fossil evidence supports the presence of leopards on Sumatra at the beginning of the Late Pleistocene, our projections are consistent with a scenario involving the extinction of leopards on Sumatra as a consequence of the Toba super volcanic eruption (similar to 74kya). The impact of this eruption was minor on Java, suggesting that leopards managed to survive here. Currently, only a few hundred leopards still live in the wild and only about 50 are managed in captivity. Therefore, this unique and distinctive subspecies requires urgent, concerted conservation efforts, integrating insitu and ex situ conservation management activities in a One Plan Approach to species conservation management.
KW  - biogeography
KW  - evolutionary history
KW  - Felidae
KW  - Southeast Asia
KW  - Toba eruption
KW  - One Plan Approach
KW  - Pleistocene
KW  - Javan leopard
Y1  - 2016
U6  - https://doi.org/10.1111/jzo.12348
SN  - 0952-8369
SN  - 1469-7998
VL  - 299
SP  - 239
EP  - 250
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Kramer, A.
A1  - Keitel, T.
A1  - Winkler, K.
A1  - Stöcklein, Walter F. M.
A1  - Hühne, Wolfgang
A1  - Schneider-Mergener, Jens
T1  - Molecular basis for the binding promiscuity of an anti-P24 (HIV-1) monoclonal antibody
Y1  - 1997
ER  - 
TY  - JOUR
A1  - Kramer, Rolf A.
A1  - Kainmüller, Eva K.
A1  - Flehr, Roman
A1  - Kumke, Michael Uwe
A1  - Bannwarth, Willi
T1  - Quenching of the long-lived Ru(II)bathophenanthroline luminescence for the detection of supramolecular interactions
Y1  - 2008
ER  - 
TY  - JOUR
A1  - Kramer, Rolf A.
A1  - Flehr, Roman
A1  - Lay, Myriam
A1  - Kumke, Michael Uwe
A1  - Bannwarth, Willi
T1  - Comparative studies of different quinoline derivatives as donors in fluorescence-resonance-energy-transfer (FRET) : systems in combination with a (Bathophenanthroline)ruthenium(II) complex as acceptor
Y1  - 2009
UR  - http://www3.interscience.wiley.com/cgi-bin/jhome/5007133/
U6  - https://doi.org/10.1002/hlca.200900235
SN  - 0018-019X
ER  - 
TY  - JOUR
A1  - Kienzler, Andrea
A1  - Flehr, Roman
A1  - Kramer, Rolf A.
A1  - Gehne, Soeren
A1  - Kumke, Michael Uwe
A1  - Bannwarth, Willi
T1  - Novel Three-Color FRET Tool Box for Advanced Protein and DNA Analysis
JF  - Bioconjugate chemistry
N2  - We report on a new three-color FRET system which we were able to verify in peptides as well as in synthetic DNA. All three chromophores could be introduced by a building block approach avoiding postsynthetic labeling. Additional features are robustness, matching spectroscopic properties, high-energy transfer, and sensitivity. The system was investigated in detail on a set of peptides as well as an array of tailored oligonucleotides. The detailed analysis of the experimental data and comparison with theoretical considerations were in excellent agreement. It is shown that in the case of polypeptides specific interaction with the fluorescence probes has to be considered. In contrast with DNA, the fluorescence probes did not show any indications of such interactions. The novel three-color FRET toolbox revealed the potential for applications studying fundamental processes of three interacting molecules in life science applications.
Y1  - 2011
U6  - https://doi.org/10.1021/bc2002659
SN  - 1043-1802
VL  - 22
IS  - 9
SP  - 1852
EP  - 1863
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Foerster, Verena
A1  - Deocampo, Daniel M.
A1  - Asrat, Asfawossen
A1  - Günter, Christina
A1  - Junginger, Annett
A1  - Krämer, Kai Hauke
A1  - Stroncik, Nicole A.
A1  - Trauth, Martin H.
T1  - Towards an understanding of climate proxy formation in the Chew Bahir basin, southern Ethiopian Rift
JF  - Palaeogeography, palaeoclimatology, palaeoecology : an international journal for the geo-sciences
N2  - Deciphering paleoclimate from lake sediments is a challenge due to the complex relationship between climate parameters and sediment composition. Here we show the links between potassium (K) concentrations in the sediments of the Chew Bahir basin in the Southern Ethiopian Rift and fluctuations in the catchment precipitation/evaporation balance. Our micro-X-ray fluorescence and X-ray diffraction results suggest that the most likely process linking climate with potassium concentrations is the authigenic illitization of smectites during episodes of higher alkalinity and salinity in the closed -basin lake, due to a drier climate. Whole-rock and clay size fraction analyses suggest that illitization of the Chew Bahir clay minerals with increasing evaporation is enhanced by octahedral Al-to-Mg substitution in the clay minerals, with the resulting layer charge increase facilitating potassium-fixation. Linking mineralogy with geochemistry shows the links between hydroclimatic control, process and formation of the Chew Bahir K patterns, in the context of well-known and widely documented eastern African climate fluctuations over the last 45,000 years. These results indicate characteristic mineral alteration patterns associated with orbitally controlled wet-dry cycles such as the African Humid Period (similar to 15-5 ka) or high-latitude controlled climate events such as the Younger Dryas (similar to 12.8-11.6 ka) chronozone. Determining the impact of authigenic mineral alteration on the Chew Bahir records enables the interpretation of the previously established pXRF-derived aridity proxy K and provides a better paleohydrological understanding of complex climate proxy formation.
KW  - Paleoclimatology
KW  - Authigenic mineral transformation
KW  - Potassium
KW  - Illitization
KW  - Zeolites
Y1  - 2018
U6  - https://doi.org/10.1016/j.palaeo.2018.04.009
SN  - 0031-0182
SN  - 1872-616X
VL  - 501
SP  - 111
EP  - 123
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Heiden, Sophia
A1  - Yue, Yanhua
A1  - Kirsch, Harald
A1  - Wirth, Jonas A.
A1  - Saalfrank, Peter
A1  - Campen, Richard Kramer
T1  - Water dissociative adsorption on α-Al2O3(112̅0) is controlled by surface site undercoordination, density, and topology
JF  - The journal of physical chemistry / publ. weekly by the American Chemical Society : C, Nanomaterials and interfaces
N2  - α-Al2O3 surfaces are common in a wide variety of applications and useful models of more complicated, environmentally abundant, alumino-silicate surfaces. While decades of work have clarified that all properties of these surfaces depend sensitively on the crystal face and the presence of even small amounts of water, quantitative insight into this dependence has proven challenging. Overcoming this challenge requires systematic study of the mechanism by which water interacts with various α-Al2O3 surfaces. Such insight is most easily gained for the interaction of small amounts of water with surfaces in ultra high vacuum. In this study, we continue our combined theoretical and experimental approach to this problem, previously applied to water interaction with the α-Al2O3 (0001) and (11̅02) surfaces, now to water interaction with the third most stable surface, that is, the (112̅0). Because we characterize all three surfaces using similar tools, it is straightforward to conclude that the (112̅0) is most reactive with water. The most important factor explaining its increased reactivity is that the high density of undercoordinated surface Al atoms on the (112̅0) surface allows the bidentate adsorption of OH fragments originating from dissociatively adsorbed water, while only monodentate adsorption is possible on the (0001) and (11̅02) surfaces: the reactivity of α-Al2O3 surfaces with water depends strongly, and nonlinearly, on the density of undercoordinated surface Al atoms.
Y1  - 2018
U6  - https://doi.org/10.1021/acs.jpcc.7b10410
SN  - 1932-7447
VL  - 122
IS  - 12
SP  - 6573
EP  - 6584
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Hocher, Berthold
A1  - Lu, Yong-Ping
A1  - Reichetzeder, Christoph
A1  - Zhang, Xiaoli
A1  - Tsuprykov, Oleg
A1  - Rahnenführer, Jan
A1  - Xie, Li
A1  - Li, Jian
A1  - Hu, Liang
A1  - Krämer, Bernhard K.
A1  - Hasan, Ahmed A.
T1  - Paternal eNOS deficiency in mice affects glucose homeostasis and liver glycogen in male offspring without inheritance of eNOS deficiency itself
JF  - Diabetologia
N2  - Aims/hypothesis It was shown that maternal endothelial nitric oxide synthase (eNOS) deficiency causes fatty liver disease and numerically lower fasting glucose in female wild-type offspring, suggesting that parental genetic variants may influence the offspring's phenotype via epigenetic modifications in the offspring despite the absence of a primary genetic defect. The aim of the current study was to analyse whether paternal eNOS deficiency may cause the same phenotype as seen with maternal eNOS deficiency. Methods Heterozygous (+/-) male eNOS (Nos3) knockout mice or wild-type male mice were bred with female wild-type mice. The phenotype of wild-type offspring of heterozygous male eNOS knockout mice was compared with offspring from wild-type parents. Results Global sperm DNA methylation decreased and sperm microRNA pattern altered substantially. Fasting glucose and liver glycogen storage were increased when analysing wild-type male and female offspring of +/- eNOS fathers. Wild-type male but not female offspring of +/- eNOS fathers had increased fasting insulin and increased insulin after glucose load. Analysing candidate genes for liver fat and carbohydrate metabolism revealed that the expression of genes encoding glucocorticoid receptor (Gr; also known as Nr3c1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1a; also known as Ppargc1a) was increased while DNA methylation of Gr exon 1A and Pgc1a promoter was decreased in the liver of male wild-type offspring of +/- eNOS fathers. The endocrine pancreas in wild-type offspring was not affected. <br /> Conclusions/interpretation Our study suggests that paternal genetic defects such as eNOS deficiency may alter the epigenome of the sperm without transmission of the paternal genetic defect itself. In later life wild-type male offspring of +/- eNOS fathers developed increased fasting insulin and increased insulin after glucose load. These effects are associated with increased Gr and Pgc1a gene expression due to altered methylation of these genes.
KW  - eNOS
KW  - Glucocorticoid receptor
KW  - Insulin resistance
KW  - Paternal programming;
KW  - PGC1a
Y1  - 2022
U6  - https://doi.org/10.1007/s00125-022-05700-x
SN  - 0012-186X
SN  - 1432-0428
VL  - 65
IS  - 7
SP  - 1222
EP  - 1236
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Trauth, Martin H.
A1  - Asrat, Asfawossen
A1  - Düsing, Walter
A1  - Foerster, Verena
A1  - Krämer, K. Hauke
A1  - Marwan, Norbert
A1  - Maslin, Mark A.
A1  - Schäbitz, Frank
T1  - Classifying past climate change in the Chew Bahir basin, southern Ethiopia, using recurrence quantification analysis
JF  - Climate dynamics : observational, theoretical and computational research on the climate system
N2  - The Chew Bahir Drilling Project (CBDP) aims to test possible linkages between climate and evolution in Africa through the analysis of sediment cores that have recorded environmental changes in the Chew Bahir basin. In this statistical project we consider the Chew Bahir palaeolake to be a dynamical system consisting of interactions between its different components, such as the waterbody, the sediment beneath lake, and the organisms living within and around the lake. Recurrence is a common feature of such dynamical systems, with recurring patterns in the state of the system reflecting typical influences. Identifying and defining these influences contributes significantly to our understanding of the dynamics of the system. Different recurring changes in precipitation, evaporation, and wind speed in the Chew Bahir basin could result in similar (but not identical) conditions in the lake (e.g., depth and area of the lake, alkalinity and salinity of the lake water, species assemblages in the water body, and diagenesis in the sediments). Recurrence plots (RPs) are graphic displays of such recurring states within a system. Measures of complexity were subsequently introduced to complement the visual inspection of recurrence plots, and provide quantitative descriptions for use in recurrence quantification analysis (RQA). We present and discuss herein results from an RQA on the environmental record from six short (< 17 m) sediment cores collected during the CBDP, spanning the last 45 kyrs. The different types of variability and transitions in these records were classified to improve our understanding of the response of the biosphere to climate change, and especially the response of humans in the area.
KW  - Paleoclimate dynamics
KW  - Eastern Africa
KW  - Pleistocene
KW  - Holocene
KW  - Time-series analysis
KW  - Recurrence plot
Y1  - 2019
U6  - https://doi.org/10.1007/s00382-019-04641-3
SN  - 0930-7575
SN  - 1432-0894
VL  - 53
IS  - 5-6
SP  - 2557
EP  - 2572
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Xiong, Yingquan
A1  - Delic, Denis
A1  - Zeng, Shufei
A1  - Chen, Xin
A1  - Chu, Chang
A1  - Hasan, Ahmed A.
A1  - Krämer, Bernhard K.
A1  - Klein, Thomas
A1  - Yin, Lianghong
A1  - Hocher, Berthold
T1  - Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy-effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker
JF  - BMC nephrology
N2  - Background Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. Methods We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. Results In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. Conclusions Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.
KW  - SARS CoV-2 host factors
KW  - 5/6 nephrectomy
KW  - High-salt diet
KW  - ARB
KW  - DPP4 inhibitor
KW  - SGLT2 blocker
Y1  - 2022
U6  - https://doi.org/10.1186/s12882-022-02747-1
SN  - 1471-2369
VL  - 23
IS  - 1
PB  - Springer Nature
CY  - London
ER  -