TY - JOUR A1 - Middeldorp, Christel M. A1 - Mahajan, Anubha A1 - Horikoshi, Momoko A1 - Robertson, Neil R. A1 - Beaumont, Robin N. A1 - Bradfield, Jonathan P. A1 - Bustamante, Mariona A1 - Cousminer, Diana L. A1 - Day, Felix R. A1 - De Silva, N. Maneka A1 - Guxens, Monica A1 - Mook-Kanamori, Dennis O. A1 - St Pourcain, Beate A1 - Warrington, Nicole M. A1 - Adair, Linda S. A1 - Ahlqvist, Emma A1 - Ahluwalia, Tarunveer Singh A1 - Almgren, Peter A1 - Ang, Wei A1 - Atalay, Mustafa A1 - Auvinen, Juha A1 - Bartels, Meike A1 - Beckmann, Jacques S. A1 - Bilbao, Jose Ramon A1 - Bond, Tom A1 - Borja, Judith B. A1 - Cavadino, Alana A1 - Charoen, Pimphen A1 - Chen, Zhanghua A1 - Coin, Lachlan A1 - Cooper, Cyrus A1 - Curtin, John A. A1 - Custovic, Adnan A1 - Das, Shikta A1 - Davies, Gareth E. A1 - Dedoussis, George V. A1 - Duijts, Liesbeth A1 - Eastwood, Peter R. A1 - Eliasen, Anders U. A1 - Elliott, Paul A1 - Eriksson, Johan G. A1 - Estivill, Xavier A1 - Fadista, Joao A1 - Fedko, Iryna O. A1 - Frayling, Timothy M. A1 - Gaillard, Romy A1 - Gauderman, W. James A1 - Geller, Frank A1 - Gilliland, Frank A1 - Gilsanz, Vincente A1 - Granell, Raquel A1 - Grarup, Niels A1 - Groop, Leif A1 - Hadley, Dexter A1 - Hakonarson, Hakon A1 - Hansen, Torben A1 - Hartman, Catharina A. A1 - Hattersley, Andrew T. A1 - Hayes, M. Geoffrey A1 - Hebebrand, Johannes A1 - Heinrich, Joachim A1 - Helgeland, Oyvind A1 - Henders, Anjali K. A1 - Henderson, John A1 - Henriksen, Tine B. A1 - Hirschhorn, Joel N. A1 - Hivert, Marie-France A1 - Hocher, Berthold A1 - Holloway, John W. A1 - Holt, Patrick A1 - Hottenga, Jouke-Jan A1 - Hypponen, Elina A1 - Iniguez, Carmen A1 - Johansson, Stefan A1 - Jugessur, Astanand A1 - Kahonen, Mika A1 - Kalkwarf, Heidi J. A1 - Kaprio, Jaakko A1 - Karhunen, Ville A1 - Kemp, John P. A1 - Kerkhof, Marjan A1 - Koppelman, Gerard H. A1 - Korner, Antje A1 - Kotecha, Sailesh A1 - Kreiner-Moller, Eskil A1 - Kulohoma, Benard A1 - Kumar, Ashish A1 - Kutalik, Zoltan A1 - Lahti, Jari A1 - Lappe, Joan M. A1 - Larsson, Henrik A1 - Lehtimaki, Terho A1 - Lewin, Alexandra M. A1 - Li, Jin A1 - Lichtenstein, Paul A1 - Lindgren, Cecilia M. A1 - Lindi, Virpi A1 - Linneberg, Allan A1 - Liu, Xueping A1 - Liu, Jun A1 - Lowe, William L. A1 - Lundstrom, Sebastian A1 - Lyytikainen, Leo-Pekka A1 - Ma, Ronald C. W. A1 - Mace, Aurelien A1 - Magi, Reedik A1 - Magnus, Per A1 - Mamun, Abdullah A. A1 - Mannikko, Minna A1 - Martin, Nicholas G. A1 - Mbarek, Hamdi A1 - McCarthy, Nina S. A1 - Medland, Sarah E. A1 - Melbye, Mads A1 - Melen, Erik A1 - Mohlke, Karen L. A1 - Monnereau, Claire A1 - Morgen, Camilla S. A1 - Morris, Andrew P. A1 - Murray, Jeffrey C. A1 - Myhre, Ronny A1 - Najman, Jackob M. A1 - Nivard, Michel G. A1 - Nohr, Ellen A. A1 - Nolte, Ilja M. A1 - Ntalla, Ioanna A1 - Oberfield, Sharon E. A1 - Oken, Emily A1 - Oldehinkel, Albertine J. A1 - Pahkala, Katja A1 - Palviainen, Teemu A1 - Panoutsopoulou, Kalliope A1 - Pedersen, Oluf A1 - Pennell, Craig E. A1 - Pershagen, Goran A1 - Pitkanen, Niina A1 - Plomin, Robert A1 - Power, Christine A1 - Prasad, Rashmi B. A1 - Prokopenko, Inga A1 - Pulkkinen, Lea A1 - Raikkonen, Katri A1 - Raitakari, Olli T. A1 - Reynolds, Rebecca M. A1 - Richmond, Rebecca C. A1 - Rivadeneira, Fernando A1 - Rodriguez, Alina A1 - Rose, Richard J. A1 - Salem, Rany A1 - Santa-Marina, Loreto A1 - Saw, Seang-Mei A1 - Schnurr, Theresia M. A1 - Scott, James G. A1 - Selzam, Saskia A1 - Shepherd, John A. A1 - Simpson, Angela A1 - Skotte, Line A1 - Sleiman, Patrick M. A. A1 - Snieder, Harold A1 - Sorensen, Thorkild I. A. A1 - Standl, Marie A1 - Steegers, Eric A. P. A1 - Strachan, David P. A1 - Straker, Leon A1 - Strandberg, Timo A1 - Taylor, Michelle A1 - Teo, Yik-Ying A1 - Thiering, Elisabeth A1 - Torrent, Maties A1 - Tyrrell, Jessica A1 - Uitterlinden, Andre G. A1 - van Beijsterveldt, Toos A1 - van der Most, Peter J. A1 - van Duijn, Cornelia M. A1 - Viikari, Jorma A1 - Vilor-Tejedor, Natalia A1 - Vogelezang, Suzanne A1 - Vonk, Judith M. A1 - Vrijkotte, Tanja G. M. A1 - Vuoksimaa, Eero A1 - Wang, Carol A. A1 - Watkins, William J. A1 - Wichmann, H-Erich A1 - Willemsen, Gonneke A1 - Williams, Gail M. A1 - Wilson, James F. A1 - Wray, Naomi R. A1 - Xu, Shujing A1 - Xu, Cheng-Jian A1 - Yaghootkar, Hanieh A1 - Yi, Lu A1 - Zafarmand, Mohammad Hadi A1 - Zeggini, Eleftheria A1 - Zemel, Babette S. A1 - Hinney, Anke A1 - Lakka, Timo A. A1 - Whitehouse, Andrew J. O. A1 - Sunyer, Jordi A1 - Widen, Elisabeth E. A1 - Feenstra, Bjarke A1 - Sebert, Sylvain A1 - Jacobsson, Bo A1 - Njolstad, Pal R. A1 - Stoltenberg, Camilla A1 - Smith, George Davey A1 - Lawlor, Debbie A. A1 - Paternoster, Lavinia A1 - Timpson, Nicholas J. A1 - Ong, Ken K. A1 - Bisgaard, Hans A1 - Bonnelykke, Klaus A1 - Jaddoe, Vincent W. V. A1 - Tiemeier, Henning A1 - Jarvelin, Marjo-Riitta A1 - Evans, David M. A1 - Perry, John R. B. A1 - Grant, Struan F. A. A1 - Boomsma, Dorret I. A1 - Freathy, Rachel M. A1 - McCarthy, Mark I. A1 - Felix, Janine F. T1 - The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia BT - design, results and future prospects JF - European journal of epidemiology N2 - The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites. KW - Genetics KW - Consortium KW - Childhood traits and disorders KW - Longitudinal Y1 - 2019 U6 - https://doi.org/10.1007/s10654-019-00502-9 SN - 0393-2990 SN - 1573-7284 VL - 34 IS - 3 SP - 279 EP - 300 PB - Springer CY - Dordrecht 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 - 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 -