Filtern
Autor*in
- Lehtimaki, Terho (4)
- Loos, Ruth J. F. (4)
- Raitakari, Olli T. (4)
- Almgren, Peter (3)
- Bakker, Stephan J. L. (3)
- Bansal, Nisha (3)
- Biggs, Mary L. (3)
- Boerwinkle, Eric (3)
- Boger, Carsten A. (3)
- Brenner, Hermann (3)
- Böttinger, Erwin (3)
- Carroll, Robert J. (3)
- Chai, Jin-Fang (3)
- Chee, Miao-Li (3)
- Chee, Miao-Ling (3)
- Cheng, Ching-Yu (3)
- Chu, Audrey Y. (3)
- Cocca, Massimiliano (3)
- Coresh, Josef (3)
- Degenhardt, Frauke (3)
- Eckardt, Kai-Uwe (3)
- Endlich, Karlhans (3)
- Feitosa, Mary F. (3)
- Foo, Valencia Hui Xian (3)
- Franke, Andre (3)
- Freitag-Wolf, Sandra (3)
- Gansevoort, Ron T. (3)
- Ghasemi, Sahar (3)
- Gieger, Christian (3)
- Gorski, Mathias (3)
- Hamet, Pavel (3)
- Heid, Iris M. (3)
- Ho, Kevin (3)
- Hofer, Edith (3)
- Hoppmann, Anselm (3)
- Horn, Katrin (3)
- Hutri-Kahonen, Nina (3)
- Hwang, Shih-Jen (3)
- Ikram, M. Arfan (3)
- Josyula, Navya Shilpa (3)
- Jung, Bettina (3)
- Kahonen, Mika (3)
- Khor, Chiea-Chuen (3)
- Kleber, Marcus E. (3)
- Koenig, Wolfgang (3)
- Kottgen, Anna (3)
- Kramer, Holly (3)
- Kronenberg, Florian (3)
- Lange, Leslie A. (3)
- Li, Man (3)
- Li, Yong (3)
- Lieb, Wolfgang (3)
- Lukas, Mary Ann (3)
- Lyytikainen, Leo-Pekka (3)
- Meisinger, Christa (3)
- Meitinger, Thomas (3)
- Melander, Olle (3)
- Milaneschi, Yuri (3)
- Mishra, Pashupati P. (3)
- Mononen, Nina (3)
- Mychaleckyj, Josyf C. (3)
- Nadkarni, Girish N. (3)
- Nauck, Matthias (3)
- Nikus, Kjell (3)
- Ning, Boting (3)
- Nolte, Ilja M. (3)
- Nutile, Teresa (3)
- Orho-Melander, Marju (3)
- Pattaro, Cristian (3)
- Pendergrass, Sarah A. (3)
- Penninx, Brenda W. J. H. (3)
- Preuss, Michael H. (3)
- Psaty, Bruce M. (3)
- Raffield, Laura M. (3)
- Rettig, Rainer (3)
- Rheinberger, Myriam (3)
- Rice, Kenneth M. (3)
- Rossing, Peter (3)
- Sabanayagam, Charumathi (3)
- Schmidt, Helena (3)
- Schmidt, Reinhold (3)
- Scholz, Markus (3)
- Schulz, Christina-Alexandra (3)
- Sedaghat, Sanaz (3)
- Shaffer, Christian M. (3)
- Sieber, Karsten B. (3)
- Snieder, Harold (3)
- Strauch, Konstantin (3)
- Szymczak, Silke (3)
- Taylor, Kent D. (3)
- Tayo, Bamidele O. (3)
- Teumer, Alexander (3)
- Thio, Chris H. L. (3)
- Tin, Adrienne (3)
- Tremblay, Johanne (3)
- Verweij, Niek (3)
- Waldenberger, Melanie (3)
- Wallentin, Lars (3)
- Waterworth, Dawn M. (3)
- Wilson, James G. (3)
- Wong, Tien-Yin (3)
- Wuttke, Matthias (3)
- Yang, Qiong (3)
- Yasuda, Masayuki (3)
- Yerges-Armstrong, Laura M. (3)
- Ahluwalia, Tarunveer S. (2)
- Banas, Bernhard (2)
- Chaker, Layal (2)
- Chalmers, John (2)
- Coassin, Stefan (2)
- Froguel, Philippe (2)
- Gampawar, Piyush (2)
- Ghanbari, Mohsen (2)
- Holleczek, Bernd (2)
- Jaddoe, Vincent W. V. (2)
- Kiess, Wieland (2)
- Kraemer, Bernhard K. (2)
- Kuehnel, Brigitte (2)
- Mahajan, Anubha (2)
- Matias-Garcia, Pamela R. (2)
- Mohlke, Karen L. (2)
- Mook-Kanamori, Dennis O. (2)
- O'Donoghue, Michelle L. (2)
- Rivadeneira, Fernando (2)
- Rosenkranz, Alexander R. (2)
- Rotter, Jerome (2)
- Schoettker, Ben (2)
- Stumvoll, Michael (2)
- Uitterlinden, Andre G. (2)
- Voelker, Uwe (2)
- Vollenweider, Peter (2)
- Wang, Judy (2)
- Wanner, Christoph (2)
- Wanner, Veronika (2)
- White, Harvey D. (2)
- Wilson, James F. (2)
- Winkler, Thomas W. (2)
- Woodward, Mark (2)
- Zhang, Yan (2)
- de Borst, Martin H. (2)
- van der Harst, Pim (2)
- van der Most, Peter J. (2)
- Adair, Linda S. (1)
- Afaq, Saima (1)
- Ahluwalia, Tarunveer Singh (1)
- Akilesh, Shreeram (1)
- Akiyama, Masato (1)
- Al-Odaib, Ali (1)
- Alkuraya, Fowzan S. (1)
- Amin, Najaf (1)
- Amouyel, Philippe (1)
- Andersson, Ehm Astrid (1)
- Arnlov, Johan (1)
- Baptista, Daniela (1)
- Barton, Sheila J. (1)
- Ben Schottker (1)
- Bennett, Amanda J. (1)
- Bergmann, Sven (1)
- Berry, Diane J. (1)
- Biino, Ginevra (1)
- Bin Wei, Wen (1)
- Bisgaard, Hans (1)
- Blakemore, Alexandra I. F. (1)
- Bochud, Murielle (1)
- Boehnke, Michael (1)
- Boissel, Mathilde (1)
- Bonnelykke, Klaus (1)
- Boomsma, Dorret I. (1)
- Boreham, Colin A. G. (1)
- Boutin, Thibaud S. (1)
- Bradfield, Jonathan P. (1)
- Brumat, Marco (1)
- Burkhardt, Ralph (1)
- Bustamante, Mariona (1)
- Butterworth, Adam S. (1)
- Buxton, Jessica L. (1)
- Campana, Eric (1)
- Campbell, Archie (1)
- Campbell, Harry (1)
- Canouil, Mickael (1)
- Catamo, Eulalia (1)
- Chambers, John C. (1)
- Charoen, Pimphen (1)
- Chasman, Daniel I. (1)
- Chen, Xu (1)
- Cheng, Yurong (1)
- Christensen, Kaare (1)
- Cifkova, Renata (1)
- Ciullo, Marina (1)
- Concas, Maria Pina (1)
- Cook, James P. (1)
- Cooper, Cyrus (1)
- Corre, Tanguy (1)
- Cousminer, Diana L. (1)
- Cusi, Daniele (1)
- Dallongeville, Jean (1)
- Danesh, John (1)
- Das, Shikta (1)
- Daw, E. Warwick (1)
- De Borst, Martin H. (1)
- De Grandi, Alessandro (1)
- De Mutsert, Renee (1)
- De Vries, Aiko P. J. (1)
- Dedoussis, George V. (1)
- Dehghan, Abbas (1)
- Delgado, Graciela (1)
- Demirkan, Ayse (1)
- Devuyst, Olivier (1)
- Di Angelantonio, Emanuele (1)
- Dittrich, Katalin (1)
- Divers, Jasmin (1)
- Dorajoo, Rajkumar (1)
- Edward, Digna R. Velez (1)
- Edwards, Todd L. (1)
- Ehret, Georg (1)
- Elliott, Paul (1)
- Eriksson, Johan G. (1)
- Estivill, Xavier (1)
- Evans, David M. (1)
- Evans, Michele K. (1)
- Feenstra, Bjarke (1)
- Felix, Janine F. (1)
- Flexeder, Claudia (1)
- Franco, Oscar H. (1)
- Frayling, Timothy M. (1)
- Freathy, Rachel M. (1)
- Freedman, Barry I. (1)
- Friedlander, Yechiel (1)
- Fuchsberger, Christian (1)
- Fulford, Anthony J. (1)
- Gao, He (1)
- Gasparini, Paolo (1)
- Gaziano, J. Michael (1)
- Geller, Frank (1)
- Giedraitis, Vilmantas (1)
- Gillman, Matthew W. (1)
- Giri, Ayush (1)
- Girotto, Giorgia (1)
- Giulianini, Franco (1)
- Godfrey, Keith M. (1)
- Gogele, Martin (1)
- Goh, Liang-Kee (1)
- Gordon, Scott D. (1)
- Gottrand, Frederic (1)
- Grant, Struan F. A. (1)
- Groves, Christopher J. (1)
- Gudbjartsson, Daniel F. (1)
- Gudnason, Vilmundur (1)
- Guxens, Monica (1)
- Hakonarson, Hakon (1)
- Haller, Toomas (1)
- Hansen, Torben (1)
- Harder, Marie N. (1)
- Harris, Tamara B. (1)
- Hartman, Catharina A. (1)
- Hattersley, Andrew T. (1)
- Hayward, Caroline (1)
- Heikkinen, Jani (1)
- Heinrich, Joachim (1)
- Hellwege, Jacklyn N. (1)
- Heng, Chew-Kiat (1)
- Hennig, Branwen J. (1)
- Hicks, Andrew A. (1)
- Hirschhorn, Joel N. (1)
- Hocher, Berthold (1)
- Hofman, Albert (1)
- Hollegaard, Mads V. (1)
- Holloway, John W. (1)
- Horikoshi, Momoko (1)
- Hottenga, Jouke-Jan (1)
- Hougaard, David M. (1)
- Huang, Wei (1)
- Hung, Adriana M. (1)
- Hyppoenen, Elina (1)
- Indridason, Olafur S. (1)
- Ingelsson, Erik (1)
- Inskip, Hazel M. (1)
- Isaacs, Aaron (1)
- Ising, Marcus (1)
- Jakobsdottir, Johanna (1)
- Jameson, Karen A. (1)
- Jarvelin, Marjo-Riitta (1)
- Jonas, Jost B. (1)
- Jorgensen, Torben (1)
- Joshi, Peter K. (1)
- Kaakinen, Marika (1)
- Kamatani, Yoichiro (1)
- Kammerer, Candace M. (1)
- Kanai, Masahiro (1)
- Kanaka-Gantenbein, Christina (1)
- Kastarinen, Mika (1)
- Kemp, John P. (1)
- Kerkhof, Marjan (1)
- Kerr, Shona M. (1)
- Kilpelainen, Tuomas O. (1)
- Kirin, Mirna (1)
- Kirsten, Holger (1)
- Klopp, Norman (1)
- Knight, Bridget A. (1)
- Koerner, Antje (1)
- Kooner, Jaspal S. (1)
- Koppelman, Gerard H. (1)
- Korner, Antje (1)
- Kovacs, Peter (1)
- Kraja, Aldi T. (1)
- Krajcoviechova, Alena (1)
- Kramer, Bernhard K. (1)
- Kreiner-Moller, Eskil (1)
- Kubo, Michiaki (1)
- Kuhnel, Brigitte (1)
- Kuokkanen, Mikko (1)
- Kutalik, Zoltan (1)
- Kuusisto, Johanna (1)
- Kuzawa, Christopher W. (1)
- La Bianca, Martina (1)
- Laakso, Markku (1)
- Lagou, Vasiliki (1)
- Lakka, Timo A. (1)
- Langefeld, Carl D. (1)
- Lawlor, Debbie A. (1)
- Lee, Jeannette Jen-Mai (1)
- Lehne, Benjamin (1)
- Lim, Su-Chi (1)
- Lind, Lars (1)
- Lindgren, Cecilia M. (1)
- Lindi, Virpi (1)
- Liu, Jianjun (1)
- Liu, Jun (1)
- Loeffler, Markus (1)
- Lucae, Susanne (1)
- Magi, Reedik (1)
- Magnusson, Patrik K. E. (1)
- Marten, Jonathan (1)
- Martin, Nicholas G. (1)
- Martins, Jade (1)
- Marz, Winfried (1)
- Mascalzoni, Deborah (1)
- Matsuda, Koichi (1)
- McCarthy, Mark I. (1)
- McMahon, George (1)
- Meirhaeghe, Aline (1)
- Melbye, Mads (1)
- Metspalu, Andres (1)
- Meyer, Brian F. (1)
- Mikaelsdottir, Evgenia K. (1)
- Miliku, Kozeta (1)
- Monies, Dorota M. (1)
- Montgomery, Grant W. (1)
- Moreno, Luis A. (1)
- Morris, Andrew P. (1)
- Nalls, Mike A. (1)
- Newnham, John P. (1)
- Niinikoski, Harri (1)
- Noce, Damia (1)
- Noordam, Raymond (1)
- Ntalla, Ioanna (1)
- Okada, Yukinori (1)
- Olafsson, Isleifur (1)
- Oldehinkel, Albertine J. (1)
- Ong, Ken K. (1)
- Oostra, Ben A. (1)
- Ouwehand, Willem H. (1)
- Padmanabhan, Sandosh (1)
- Palmer, Nicholette D. (1)
- Palsson, Runolfur (1)
- Parsa, Afshin (1)
- Pearson, Ewan R. (1)
- Pedersen, Louise (1)
- Pedersen, Oluf (1)
- Pennell, Craig E. (1)
- Perls, Thomas (1)
- Perola, Markus (1)
- Pfab, Thiemo (1)
- Pirastu, Mario (1)
- Pirastu, Nicola (1)
- Pistis, Giorgio (1)
- Podgornaia, Anna I. (1)
- Polasek, Ozren (1)
- Ponte, Belen (1)
- Porteous, David J. (1)
- Postma, Dirkje S. (1)
- Poulain, Tanja (1)
- Pouta, Anneli (1)
- Power, Chris (1)
- Pramstaller, Peter P. (1)
- Prentice, Andrew M. (1)
- Prins, Bram P. (1)
- Program, V. A. Million Veteran (1)
- Prokopenko, Inga (1)
- Province, Michael A. (1)
- Rabelink, Ton J. (1)
- Reilly, Dermot F. (1)
- Ridker, Paul M. (1)
- Ring, Susan M. (1)
- Rizzi, Federica (1)
- Roberts, David J. (1)
- Robertson, Neil R. (1)
- Robino, Antonietta (1)
- Rotter, Jerome I. (1)
- Rudan, Igor (1)
- Rueedi, Rico (1)
- Ruggiero, Daniela (1)
- Ryan, Kathleen A. (1)
- Saarinen, Maiju (1)
- Saba, Yasaman (1)
- Sala, Cinzia Felicita (1)
- Salem, Rany M. (1)
- Salomaa, Veikko (1)
- Salvi, Erika (1)
- Saum, Kai-Uwe (1)
- Saw, Seang-Mei (1)
- Schupf, Nicole (1)
- Sebert, Sylvain (1)
- Shi, Yuan (1)
- Shields, Beverley M. (1)
- Sim, Xueling (1)
- Simell, Olli (1)
- Slowinski, Torsten (1)
- Smith, Albert V. (1)
- Smith, Blair H. (1)
- Smith, George Davey (1)
- Soranzo, Nicole (1)
- Sovio, Ulla (1)
- Spracklen, Cassandra N. (1)
- St Pourcain, Beate (1)
- Stefansson, Kari (1)
- Stringham, Heather M. (1)
- Sveinbjornsson, Gardar (1)
- Svensson, Per O. (1)
- Taal, H. Rob (1)
- Tai, E-Shyong (1)
- Tajuddin, Salman M. (1)
- Tan, Nicholas Y. Q. (1)
- Teren, Andrej (1)
- Tham, Yih-Chung (1)
- Thiering, Elisabeth (1)
- Thiery, Joachim (1)
- Thomsen, Hauke (1)
- Thorleifsson, Gudmar (1)
- Tiesler, Carla M. T. (1)
- Timpson, Nicholas J. (1)
- Toenjes, Anke (1)
- Toniolo, Daniela (1)
- Tonjes, Anke (1)
- Tzoulaki, Ioanna (1)
- Vaag, Allan (1)
- Vaccargiu, Simona (1)
- Van Dam, Rob M. (1)
- Van Duijn, Cornelia M. (1)
- Van der Harst, Pim (1)
- Van der Most, Peter J. (1)
- Viikari, Jorma S. (1)
- Vink, Jacqueline M. (1)
- Vissing, Nadja Hawwa (1)
- Vitart, Veronique (1)
- Vogelezang, Suzanne (1)
- Volker, Uwe (1)
- Waeber, Gerard (1)
- Wang, Chaolong (1)
- Wang, Lihua (1)
- Wang, Ya Xing (1)
- Wareham, Nicholas J. (1)
- Warrington, Nicole M. (1)
- White, Harvey (1)
- Whitfield, John B. (1)
- Widen, Elisabeth (1)
- Wild, Sarah H. (1)
- Willemsen, Gonneke (1)
- Witte, Daniel R. (1)
- Wojczynski, Mary K. (1)
- Wong, Charlene (1)
- Wu, Ying (1)
- Xu, Liang (1)
- Xu, Yizhe (1)
- Yaghootkar, Hanieh (1)
- Yu, Zhi (1)
- Zhang, Haitao (1)
- Zhang, Weihua (1)
- Zhao, Jianhua (1)
- Zhao, Jing Hua (1)
- Zhou, Kaixin (1)
- Zonderman, Alan B. (1)
- de Geus, Eco J. C. (1)
- den Hoed, Marcel (1)
- van Duijn, Cornelia M. (1)
- van Leeuwen, Elisabeth M. (1)
Dokumenttyp
- Wissenschaftlicher Artikel (3)
- Postprint (1)
Sprache
- Englisch (4)
Gehört zur Bibliographie
- ja (4)
Schlagworte
- acute kidney injury (2)
- end-stage kidney disease (2)
- genome-wide association (2)
- rapid eGFRcrea decline (2)
- study (2)
Gorski, Mathias ; Jung, Bettina ; Li, Yong ; Matias-Garcia, Pamela R. ; Wuttke, Matthias ; Coassin, Stefan ; Thio, Chris H. L. ; Kleber, Marcus E. ; Winkler, Thomas W. ; Wanner, Veronika ; Chai, Jin-Fang ; Chu, Audrey Y. ; Cocca, Massimiliano ; Feitosa, Mary F. ; Ghasemi, Sahar ; Hoppmann, Anselm ; Horn, Katrin ; Li, Man ; Nutile, Teresa ; Scholz, Markus ; Sieber, Karsten B. ; Teumer, Alexander ; Tin, Adrienne ; Wang, Judy ; Tayo, Bamidele O. ; Ahluwalia, Tarunveer S. ; Almgren, Peter ; Bakker, Stephan J. L. ; Banas, Bernhard ; Bansal, Nisha ; Biggs, Mary L. ; Boerwinkle, Eric ; Böttinger, Erwin ; Brenner, Hermann ; Carroll, Robert J. ; Chalmers, John ; Chee, Miao-Li ; Chee, Miao-Ling ; Cheng, Ching-Yu ; Coresh, Josef ; de Borst, Martin H. ; Degenhardt, Frauke ; Eckardt, Kai-Uwe ; Endlich, Karlhans ; Franke, Andre ; Freitag-Wolf, Sandra ; Gampawar, Piyush ; Gansevoort, Ron T. ; Ghanbari, Mohsen ; Gieger, Christian ; Hamet, Pavel ; Ho, Kevin ; Hofer, Edith ; Holleczek, Bernd ; Foo, Valencia Hui Xian ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Josyula, Navya Shilpa ; Kahonen, Mika ; Khor, Chiea-Chuen ; Koenig, Wolfgang ; Kramer, Holly ; Kraemer, Bernhard K. ; Kuehnel, Brigitte ; Lange, Leslie A. ; Lehtimaki, Terho ; Lieb, Wolfgang ; Loos, Ruth J. F. ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Milaneschi, Yuri ; Mishra, Pashupati P. ; Mononen, Nina ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; O'Donoghue, Michelle L. ; Orho-Melander, Marju ; Pendergrass, Sarah A. ; Penninx, Brenda W. J. H. ; Preuss, Michael H. ; Psaty, Bruce M. ; Raffield, Laura M. ; Raitakari, Olli T. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Rosenkranz, Alexander R. ; Rossing, Peter ; Rotter, Jerome ; Sabanayagam, Charumathi ; Schmidt, Helena ; Schmidt, Reinhold ; Schoettker, Ben ; Schulz, Christina-Alexandra ; Sedaghat, Sanaz ; Shaffer, Christian M. ; Strauch, Konstantin ; Szymczak, Silke ; Taylor, Kent D. ; Tremblay, Johanne ; Chaker, Layal ; van der Harst, Pim ; van der Most, Peter J. ; Verweij, Niek ; Voelker, Uwe ; Waldenberger, Melanie ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey D. ; Wilson, James G. ; Wong, Tien-Yin ; Woodward, Mark ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Yan ; Snieder, Harold ; Wanner, Christoph ; Boger, Carsten A. ; Kottgen, Anna ; Kronenberg, Florian ; Pattaro, Cristian ; Heid, Iris M.
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.
Gorski, Mathias ; Jung, Bettina ; Li, Yong ; Matias-Garcia, Pamela R. ; Wuttke, Matthias ; Coassin, Stefan ; Thio, Chris H. L. ; Kleber, Marcus E. ; Winkler, Thomas W. ; Wanner, Veronika ; Chai, Jin-Fang ; Chu, Audrey Y. ; Cocca, Massimiliano ; Feitosa, Mary F. ; Ghasemi, Sahar ; Hoppmann, Anselm ; Horn, Katrin ; Li, Man ; Nutile, Teresa ; Scholz, Markus ; Sieber, Karsten B. ; Teumer, Alexander ; Tin, Adrienne ; Wang, Judy ; Tayo, Bamidele O. ; Ahluwalia, Tarunveer S. ; Almgren, Peter ; Bakker, Stephan J. L. ; Banas, Bernhard ; Bansal, Nisha ; Biggs, Mary L. ; Boerwinkle, Eric ; Böttinger, Erwin ; Brenner, Hermann ; Carroll, Robert J. ; Chalmers, John ; Chee, Miao-Li ; Chee, Miao-Ling ; Cheng, Ching-Yu ; Coresh, Josef ; de Borst, Martin H. ; Degenhardt, Frauke ; Eckardt, Kai-Uwe ; Endlich, Karlhans ; Franke, Andre ; Freitag-Wolf, Sandra ; Gampawar, Piyush ; Gansevoort, Ron T. ; Ghanbari, Mohsen ; Gieger, Christian ; Hamet, Pavel ; Ho, Kevin ; Hofer, Edith ; Holleczek, Bernd ; Foo, Valencia Hui Xian ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Josyula, Navya Shilpa ; Kahonen, Mika ; Khor, Chiea-Chuen ; Koenig, Wolfgang ; Kramer, Holly ; Kraemer, Bernhard K. ; Kuehnel, Brigitte ; Lange, Leslie A. ; Lehtimaki, Terho ; Lieb, Wolfgang ; Loos, Ruth J. F. ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Milaneschi, Yuri ; Mishra, Pashupati P. ; Mononen, Nina ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; O'Donoghue, Michelle L. ; Orho-Melander, Marju ; Pendergrass, Sarah A. ; Penninx, Brenda W. J. H. ; Preuss, Michael H. ; Psaty, Bruce M. ; Raffield, Laura M. ; Raitakari, Olli T. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Rosenkranz, Alexander R. ; Rossing, Peter ; Rotter, Jerome ; Sabanayagam, Charumathi ; Schmidt, Helena ; Schmidt, Reinhold ; Schoettker, Ben ; Schulz, Christina-Alexandra ; Sedaghat, Sanaz ; Shaffer, Christian M. ; Strauch, Konstantin ; Szymczak, Silke ; Taylor, Kent D. ; Tremblay, Johanne ; Chaker, Layal ; van der Harst, Pim ; van der Most, Peter J. ; Verweij, Niek ; Voelker, Uwe ; Waldenberger, Melanie ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey D. ; Wilson, James G. ; Wong, Tien-Yin ; Woodward, Mark ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Yan ; Snieder, Harold ; Wanner, Christoph ; Boger, Carsten A. ; Kottgen, Anna ; Kronenberg, Florian ; Pattaro, Cristian ; Heid, Iris M.
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.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Wuttke, Matthias ; Li, Yong ; Li, Man ; Sieber, Karsten B. ; Feitosa, Mary F. ; Gorski, Mathias ; Tin, Adrienne ; Wang, Lihua ; Chu, Audrey Y. ; Hoppmann, Anselm ; Kirsten, Holger ; Giri, Ayush ; Chai, Jin-Fang ; Sveinbjornsson, Gardar ; Tayo, Bamidele O. ; Nutile, Teresa ; Fuchsberger, Christian ; Marten, Jonathan ; Cocca, Massimiliano ; Ghasemi, Sahar ; Xu, Yizhe ; Horn, Katrin ; Noce, Damia ; Van der Most, Peter J. ; Sedaghat, Sanaz ; Yu, Zhi ; Akiyama, Masato ; Afaq, Saima ; Ahluwalia, Tarunveer Singh ; Almgren, Peter ; Amin, Najaf ; Arnlov, Johan ; Bakker, Stephan J. L. ; Bansal, Nisha ; Baptista, Daniela ; Bergmann, Sven ; Biggs, Mary L. ; Biino, Ginevra ; Boehnke, Michael ; Boerwinkle, Eric ; Boissel, Mathilde ; Böttinger, Erwin ; Boutin, Thibaud S. ; Brenner, Hermann ; Brumat, Marco ; Burkhardt, Ralph ; Butterworth, Adam S. ; Campana, Eric ; Campbell, Archie ; Campbell, Harry ; Canouil, Mickael ; Carroll, Robert J. ; Catamo, Eulalia ; Chambers, John C. ; Chee, Miao-Ling ; Chee, Miao-Li ; Chen, Xu ; Cheng, Ching-Yu ; Cheng, Yurong ; Christensen, Kaare ; Cifkova, Renata ; Ciullo, Marina ; Concas, Maria Pina ; Cook, James P. ; Coresh, Josef ; Corre, Tanguy ; Sala, Cinzia Felicita ; Cusi, Daniele ; Danesh, John ; Daw, E. Warwick ; De Borst, Martin H. ; De Grandi, Alessandro ; De Mutsert, Renee ; De Vries, Aiko P. J. ; Degenhardt, Frauke ; Delgado, Graciela ; Demirkan, Ayse ; Di Angelantonio, Emanuele ; Dittrich, Katalin ; Divers, Jasmin ; Dorajoo, Rajkumar ; Eckardt, Kai-Uwe ; Ehret, Georg ; Elliott, Paul ; Endlich, Karlhans ; Evans, Michele K. ; Felix, Janine F. ; Foo, Valencia Hui Xian ; Franco, Oscar H. ; Franke, Andre ; Freedman, Barry I. ; Freitag-Wolf, Sandra ; Friedlander, Yechiel ; Froguel, Philippe ; Gansevoort, Ron T. ; Gao, He ; Gasparini, Paolo ; Gaziano, J. Michael ; Giedraitis, Vilmantas ; Gieger, Christian ; Girotto, Giorgia ; Giulianini, Franco ; Gogele, Martin ; Gordon, Scott D. ; Gudbjartsson, Daniel F. ; Gudnason, Vilmundur ; Haller, Toomas ; Hamet, Pavel ; Harris, Tamara B. ; Hartman, Catharina A. ; Hayward, Caroline ; Hellwege, Jacklyn N. ; Heng, Chew-Kiat ; Hicks, Andrew A. ; Hofer, Edith ; Huang, Wei ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Indridason, Olafur S. ; Ingelsson, Erik ; Ising, Marcus ; Jaddoe, Vincent W. V. ; Jakobsdottir, Johanna ; Jonas, Jost B. ; Joshi, Peter K. ; Josyula, Navya Shilpa ; Jung, Bettina ; Kahonen, Mika ; Kamatani, Yoichiro ; Kammerer, Candace M. ; Kanai, Masahiro ; Kastarinen, Mika ; Kerr, Shona M. ; Khor, Chiea-Chuen ; Kiess, Wieland ; Kleber, Marcus E. ; Koenig, Wolfgang ; Kooner, Jaspal S. ; Korner, Antje ; Kovacs, Peter ; Kraja, Aldi T. ; Krajcoviechova, Alena ; Kramer, Holly ; Kramer, Bernhard K. ; Kronenberg, Florian ; Kubo, Michiaki ; Kuhnel, Brigitte ; Kuokkanen, Mikko ; Kuusisto, Johanna ; La Bianca, Martina ; Laakso, Markku ; Lange, Leslie A. ; Langefeld, Carl D. ; Lee, Jeannette Jen-Mai ; Lehne, Benjamin ; Lehtimaki, Terho ; Lieb, Wolfgang ; Lim, Su-Chi ; Lind, Lars ; Lindgren, Cecilia M. ; Liu, Jun ; Liu, Jianjun ; Loeffler, Markus ; Loos, Ruth J. F. ; Lucae, Susanne ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Magi, Reedik ; Magnusson, Patrik K. E. ; Mahajan, Anubha ; Martin, Nicholas G. ; Martins, Jade ; Marz, Winfried ; Mascalzoni, Deborah ; Matsuda, Koichi ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Metspalu, Andres ; Mikaelsdottir, Evgenia K. ; Milaneschi, Yuri ; Miliku, Kozeta ; Mishra, Pashupati P. ; Program, V. A. Million Veteran ; Mohlke, Karen L. ; Mononen, Nina ; Montgomery, Grant W. ; Mook-Kanamori, Dennis O. ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nalls, Mike A. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; Noordam, Raymond ; Olafsson, Isleifur ; Oldehinkel, Albertine J. ; Orho-Melander, Marju ; Ouwehand, Willem H. ; Padmanabhan, Sandosh ; Palmer, Nicholette D. ; Palsson, Runolfur ; Penninx, Brenda W. J. H. ; Perls, Thomas ; Perola, Markus ; Pirastu, Mario ; Pirastu, Nicola ; Pistis, Giorgio ; Podgornaia, Anna I. ; Polasek, Ozren ; Ponte, Belen ; Porteous, David J. ; Poulain, Tanja ; Pramstaller, Peter P. ; Preuss, Michael H. ; Prins, Bram P. ; Province, Michael A. ; Rabelink, Ton J. ; Raffield, Laura M. ; Raitakari, Olli T. ; Reilly, Dermot F. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Ridker, Paul M. ; Rivadeneira, Fernando ; Rizzi, Federica ; Roberts, David J. ; Robino, Antonietta ; Rossing, Peter ; Rudan, Igor ; Rueedi, Rico ; Ruggiero, Daniela ; Ryan, Kathleen A. ; Saba, Yasaman ; Sabanayagam, Charumathi ; Salomaa, Veikko ; Salvi, Erika ; Saum, Kai-Uwe ; Schmidt, Helena ; Schmidt, Reinhold ; Ben Schottker ; Schulz, Christina-Alexandra ; Schupf, Nicole ; Shaffer, Christian M. ; Shi, Yuan ; Smith, Albert V. ; Smith, Blair H. ; Soranzo, Nicole ; Spracklen, Cassandra N. ; Strauch, Konstantin ; Stringham, Heather M. ; Stumvoll, Michael ; Svensson, Per O. ; Szymczak, Silke ; Tai, E-Shyong ; Tajuddin, Salman M. ; Tan, Nicholas Y. Q. ; Taylor, Kent D. ; Teren, Andrej ; Tham, Yih-Chung ; Thiery, Joachim ; Thio, Chris H. L. ; Thomsen, Hauke ; Thorleifsson, Gudmar ; Toniolo, Daniela ; Tonjes, Anke ; Tremblay, Johanne ; Tzoulaki, Ioanna ; Uitterlinden, Andre G. ; Vaccargiu, Simona ; Van Dam, Rob M. ; Van der Harst, Pim ; Van Duijn, Cornelia M. ; Edward, Digna R. Velez ; Verweij, Niek ; Vogelezang, Suzanne ; Volker, Uwe ; Vollenweider, Peter ; Waeber, Gerard ; Waldenberger, Melanie ; Wallentin, Lars ; Wang, Ya Xing ; Wang, Chaolong ; Waterworth, Dawn M. ; Bin Wei, Wen ; White, Harvey ; Whitfield, John B. ; Wild, Sarah H. ; Wilson, James F. ; Wojczynski, Mary K. ; Wong, Charlene ; Wong, Tien-Yin ; Xu, Liang ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Weihua ; Zonderman, Alan B. ; Rotter, Jerome I. ; Bochud, Murielle ; Psaty, Bruce M. ; Vitart, Veronique ; Wilson, James G. ; Dehghan, Abbas ; Parsa, Afshin ; Chasman, Daniel I. ; Ho, Kevin ; Morris, Andrew P. ; Devuyst, Olivier ; Akilesh, Shreeram ; Pendergrass, Sarah A. ; Sim, Xueling ; Boger, Carsten A. ; Okada, Yukinori ; Edwards, Todd L. ; Snieder, Harold ; Stefansson, Kari ; Hung, Adriana M. ; Heid, Iris M. ; Scholz, Markus ; Teumer, Alexander ; Kottgen, Anna ; Pattaro, Cristian
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.
Horikoshi, Momoko ; Yaghootkar, Hanieh ; Mook-Kanamori, Dennis O. ; Sovio, Ulla ; Taal, H. Rob ; Hennig, Branwen J. ; Bradfield, Jonathan P. ; St Pourcain, Beate ; Evans, David M. ; Charoen, Pimphen ; Kaakinen, Marika ; Cousminer, Diana L. ; Lehtimaki, Terho ; Kreiner-Moller, Eskil ; Warrington, Nicole M. ; Bustamante, Mariona ; Feenstra, Bjarke ; Berry, Diane J. ; Thiering, Elisabeth ; Pfab, Thiemo ; Barton, Sheila J. ; Shields, Beverley M. ; Kerkhof, Marjan ; van Leeuwen, Elisabeth M. ; Fulford, Anthony J. ; Kutalik, Zoltan ; Zhao, Jing Hua ; den Hoed, Marcel ; Mahajan, Anubha ; Lindi, Virpi ; Goh, Liang-Kee ; Hottenga, Jouke-Jan ; Wu, Ying ; Raitakari, Olli T. ; Harder, Marie N. ; Meirhaeghe, Aline ; Ntalla, Ioanna ; Salem, Rany M. ; Jameson, Karen A. ; Zhou, Kaixin ; Monies, Dorota M. ; Lagou, Vasiliki ; Kirin, Mirna ; Heikkinen, Jani ; Adair, Linda S. ; Alkuraya, Fowzan S. ; Al-Odaib, Ali ; Amouyel, Philippe ; Andersson, Ehm Astrid ; Bennett, Amanda J. ; Blakemore, Alexandra I. F. ; Buxton, Jessica L. ; Dallongeville, Jean ; Das, Shikta ; de Geus, Eco J. C. ; Estivill, Xavier ; Flexeder, Claudia ; Froguel, Philippe ; Geller, Frank ; Godfrey, Keith M. ; Gottrand, Frederic ; Groves, Christopher J. ; Hansen, Torben ; Hirschhorn, Joel N. ; Hofman, Albert ; Hollegaard, Mads V. ; Hougaard, David M. ; Hyppoenen, Elina ; Inskip, Hazel M. ; Isaacs, Aaron ; Jorgensen, Torben ; Kanaka-Gantenbein, Christina ; Kemp, John P. ; Kiess, Wieland ; Kilpelainen, Tuomas O. ; Klopp, Norman ; Knight, Bridget A. ; Kuzawa, Christopher W. ; McMahon, George ; Newnham, John P. ; Niinikoski, Harri ; Oostra, Ben A. ; Pedersen, Louise ; Postma, Dirkje S. ; Ring, Susan M. ; Rivadeneira, Fernando ; Robertson, Neil R. ; Sebert, Sylvain ; Simell, Olli ; Slowinski, Torsten ; Tiesler, Carla M. T. ; Toenjes, Anke ; Vaag, Allan ; Viikari, Jorma S. ; Vink, Jacqueline M. ; Vissing, Nadja Hawwa ; Wareham, Nicholas J. ; Willemsen, Gonneke ; Witte, Daniel R. ; Zhang, Haitao ; Zhao, Jianhua ; Wilson, James F. ; Stumvoll, Michael ; Prentice, Andrew M. ; Meyer, Brian F. ; Pearson, Ewan R. ; Boreham, Colin A. G. ; Cooper, Cyrus ; Gillman, Matthew W. ; Dedoussis, George V. ; Moreno, Luis A. ; Pedersen, Oluf ; Saarinen, Maiju ; Mohlke, Karen L. ; Boomsma, Dorret I. ; Saw, Seang-Mei ; Lakka, Timo A. ; Koerner, Antje ; Loos, Ruth J. F. ; Ong, Ken K. ; Vollenweider, Peter ; van Duijn, Cornelia M. ; Koppelman, Gerard H. ; Hattersley, Andrew T. ; Holloway, John W. ; Hocher, Berthold ; Heinrich, Joachim ; Power, Chris ; Melbye, Mads ; Guxens, Monica ; Pennell, Craig E. ; Bonnelykke, Klaus ; Bisgaard, Hans ; Eriksson, Johan G. ; Widen, Elisabeth ; Hakonarson, Hakon ; Uitterlinden, Andre G. ; Pouta, Anneli ; Lawlor, Debbie A. ; Smith, George Davey ; Frayling, Timothy M. ; McCarthy, Mark I. ; Grant, Struan F. A. ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; Timpson, Nicholas J. ; Prokopenko, Inga ; Freathy, Rachel M.
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
- 1 bis 4