Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-50042 Wissenschaftlicher Artikel Middeldorp, Christel M.; Mahajan, Anubha; Horikoshi, Momoko; Robertson, Neil R.; Beaumont, Robin N.; Bradfield, Jonathan P.; Bustamante, Mariona; Cousminer, Diana L.; Day, Felix R.; De Silva, N. Maneka; Guxens, Monica; Mook-Kanamori, Dennis O.; St Pourcain, Beate; Warrington, Nicole M.; Adair, Linda S.; Ahlqvist, Emma; Ahluwalia, Tarunveer Singh; Almgren, Peter; Ang, Wei; Atalay, Mustafa; Auvinen, Juha; Bartels, Meike; Beckmann, Jacques S.; Bilbao, Jose Ramon; Bond, Tom; Borja, Judith B.; Cavadino, Alana; Charoen, Pimphen; Chen, Zhanghua; Coin, Lachlan; Cooper, Cyrus; Curtin, John A.; Custovic, Adnan; Das, Shikta; Davies, Gareth E.; Dedoussis, George V.; Duijts, Liesbeth; Eastwood, Peter R.; Eliasen, Anders U.; Elliott, Paul; Eriksson, Johan G.; Estivill, Xavier; Fadista, Joao; Fedko, Iryna O.; Frayling, Timothy M.; Gaillard, Romy; Gauderman, W. James; Geller, Frank; Gilliland, Frank; Gilsanz, Vincente; Granell, Raquel; Grarup, Niels; Groop, Leif; Hadley, Dexter; Hakonarson, Hakon; Hansen, Torben; Hartman, Catharina A.; Hattersley, Andrew T.; Hayes, M. Geoffrey; Hebebrand, Johannes; Heinrich, Joachim; Helgeland, Oyvind; Henders, Anjali K.; Henderson, John; Henriksen, Tine B.; Hirschhorn, Joel N.; Hivert, Marie-France; Hocher, Berthold; Holloway, John W.; Holt, Patrick; Hottenga, Jouke-Jan; Hypponen, Elina; Iniguez, Carmen; Johansson, Stefan; Jugessur, Astanand; Kahonen, Mika; Kalkwarf, Heidi J.; Kaprio, Jaakko; Karhunen, Ville; Kemp, John P.; Kerkhof, Marjan; Koppelman, Gerard H.; Korner, Antje; Kotecha, Sailesh; Kreiner-Moller, Eskil; Kulohoma, Benard; Kumar, Ashish; Kutalik, Zoltan; Lahti, Jari; Lappe, Joan M.; Larsson, Henrik; Lehtimaki, Terho; Lewin, Alexandra M.; Li, Jin; Lichtenstein, Paul; Lindgren, Cecilia M.; Lindi, Virpi; Linneberg, Allan; Liu, Xueping; Liu, Jun; Lowe, William L.; Lundstrom, Sebastian; Lyytikainen, Leo-Pekka; Ma, Ronald C. W.; Mace, Aurelien; Magi, Reedik; Magnus, Per; Mamun, Abdullah A.; Mannikko, Minna; Martin, Nicholas G.; Mbarek, Hamdi; McCarthy, Nina S.; Medland, Sarah E.; Melbye, Mads; Melen, Erik; Mohlke, Karen L.; Monnereau, Claire; Morgen, Camilla S.; Morris, Andrew P.; Murray, Jeffrey C.; Myhre, Ronny; Najman, Jackob M.; Nivard, Michel G.; Nohr, Ellen A.; Nolte, Ilja M.; Ntalla, Ioanna; Oberfield, Sharon E.; Oken, Emily; Oldehinkel, Albertine J.; Pahkala, Katja; Palviainen, Teemu; Panoutsopoulou, Kalliope; Pedersen, Oluf; Pennell, Craig E.; Pershagen, Goran; Pitkanen, Niina; Plomin, Robert; Power, Christine; Prasad, Rashmi B.; Prokopenko, Inga; Pulkkinen, Lea; Raikkonen, Katri; Raitakari, Olli T.; Reynolds, Rebecca M.; Richmond, Rebecca C.; Rivadeneira, Fernando; Rodriguez, Alina; Rose, Richard J.; Salem, Rany; Santa-Marina, Loreto; Saw, Seang-Mei; Schnurr, Theresia M.; Scott, James G.; Selzam, Saskia; Shepherd, John A.; Simpson, Angela; Skotte, Line; Sleiman, Patrick M. A.; Snieder, Harold; Sorensen, Thorkild I. A.; Standl, Marie; Steegers, Eric A. P.; Strachan, David P.; Straker, Leon; Strandberg, Timo; Taylor, Michelle; Teo, Yik-Ying; Thiering, Elisabeth; Torrent, Maties; Tyrrell, Jessica; Uitterlinden, Andre G.; van Beijsterveldt, Toos; van der Most, Peter J.; van Duijn, Cornelia M.; Viikari, Jorma; Vilor-Tejedor, Natalia; Vogelezang, Suzanne; Vonk, Judith M.; Vrijkotte, Tanja G. M.; Vuoksimaa, Eero; Wang, Carol A.; Watkins, William J.; Wichmann, H-Erich; Willemsen, Gonneke; Williams, Gail M.; Wilson, James F.; Wray, Naomi R.; Xu, Shujing; Xu, Cheng-Jian; Yaghootkar, Hanieh; Yi, Lu; Zafarmand, Mohammad Hadi; Zeggini, Eleftheria; Zemel, Babette S.; Hinney, Anke; Lakka, Timo A.; Whitehouse, Andrew J. O.; Sunyer, Jordi; Widen, Elisabeth E.; Feenstra, Bjarke; Sebert, Sylvain; Jacobsson, Bo; Njolstad, Pal R.; Stoltenberg, Camilla; Smith, George Davey; Lawlor, Debbie A.; Paternoster, Lavinia; Timpson, Nicholas J.; Ong, Ken K.; Bisgaard, Hans; Bonnelykke, Klaus; Jaddoe, Vincent W. V.; Tiemeier, Henning; Jarvelin, Marjo-Riitta; Evans, David M.; Perry, John R. B.; Grant, Struan F. A.; Boomsma, Dorret I.; Freathy, Rachel M.; McCarthy, Mark I.; Felix, Janine F. The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia 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. Dordrecht Springer 2019 22 European journal of epidemiology 34 3 279 300 10.1007/s10654-019-00502-9 Institut für Biochemie und Biologie OPUS4-49198 Wissenschaftlicher Artikel 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 A catalog of genetic loci associated with kidney function from analyses of a million individuals 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. New York Nature Publ. Group 2019 19 Nature genetics 51 6 957 + 10.1038/s41588-019-0407-x Hasso-Plattner-Institut für Digital Engineering GmbH OPUS4-56537 misc 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. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline 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. 2020 14 Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät 19 urn:nbn:de:kobv:517-opus4-565379 10.25932/publishup-56537 Hasso-Plattner-Institut für Digital Engineering GmbH OPUS4-56536 Wissenschaftlicher Artikel 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. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline 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. New York Elsevier 2020 14 Kidney international : official journal of the International Society of Nephrology 99 4 926 939 10.1016/j.kint.2020.09.030 Hasso-Plattner-Institut für Digital Engineering GmbH