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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.
Ehl, Birgit ; Paul, Michele ; Bruns, Gunnar ; Fleischhauer, Elisabeth ; Vock, Miriam ; Gronostaj, Anna ; Grosche, Michael
Ein diagnostisches Ziel der „Profilanalyse nach Grießhaber“ ist die Testung der grammatischen Fähigkeit zur Verbstellung im Deutschen. Zur erstmaligen Evaluation der Testgüte wurden 403 ein- und mehrsprachige Grundschulkinder randomisiert drei verschiedenen Testmaterialien zugewiesen: Testmaterial, das die Zielkompetenz spezifisch stimulierte, führte zu den besten Testergebnissen. Dies spricht für eine geringe Durchführungsobjektivität. Zudem wurden Deckeneffekte für Grundschulkinder nachgewiesen, weshalb die Profilanalyse nur wenig zwischen den Grammatikfähigkeiten der Kinder differenzieren kann. Auch die Retest-Reliabilität und Auswertungsobjektivität sind noch zu gering. Zusammenfassend wird die Testgüte hinsichtlich aller betrachteten Testgütekriterien als verbesserungswürdig bewertet. Daraus werden die Empfehlungen abgeleitet, die Profilanalyse stärker zu standardisieren und um sensitivere diagnostische Kriterien für das Grundschulalter zu ergänzen. Weitere Ziele der Profilanalyse, z. B. die Verbesserung diagnostischer Kompetenzen von Lehrkräften, sind in Folgeprojekten zu evaluieren.
Aarts, Alexander A. ; Anderson, Joanna E. ; Anderson, Christopher J. ; Attridge, Peter R. ; Attwood, Angela ; Axt, Jordan ; Babel, Molly ; Bahnik, Stepan ; Baranski, Erica ; Barnett-Cowan, Michael ; Bartmess, Elizabeth ; Beer, Jennifer ; Bell, Raoul ; Bentley, Heather ; Beyan, Leah ; Binion, Grace ; Borsboom, Denny ; Bosch, Annick ; Bosco, Frank A. ; Bowman, Sara D. ; Brandt, Mark J. ; Braswell, Erin ; Brohmer, Hilmar ; Brown, Benjamin T. ; Brown, Kristina ; Bruening, Jovita ; Calhoun-Sauls, Ann ; Callahan, Shannon P. ; Chagnon, Elizabeth ; Chandler, Jesse ; Chartier, Christopher R. ; Cheung, Felix ; Christopherson, Cody D. ; Cillessen, Linda ; Clay, Russ ; Cleary, Hayley ; Cloud, Mark D. ; Cohn, Michael ; Cohoon, Johanna ; Columbus, Simon ; Cordes, Andreas ; Costantini, Giulio ; Alvarez, Leslie D. Cramblet ; Cremata, Ed ; Crusius, Jan ; DeCoster, Jamie ; DeGaetano, Michelle A. ; Della Penna, Nicolas ; den Bezemer, Bobby ; Deserno, Marie K. ; Devitt, Olivia ; Dewitte, Laura ; Dobolyi, David G. ; Dodson, Geneva T. ; Donnellan, M. Brent ; Donohue, Ryan ; Dore, Rebecca A. ; Dorrough, Angela ; Dreber, Anna ; Dugas, Michelle ; Dunn, Elizabeth W. ; Easey, Kayleigh ; Eboigbe, Sylvia ; Eggleston, Casey ; Embley, Jo ; Epskamp, Sacha ; Errington, Timothy M. ; Estel, Vivien ; Farach, Frank J. ; Feather, Jenelle ; Fedor, Anna ; Fernandez-Castilla, Belen ; Fiedler, Susann ; Field, James G. ; Fitneva, Stanka A. ; Flagan, Taru ; Forest, Amanda L. ; Forsell, Eskil ; Foster, Joshua D. ; Frank, Michael C. ; Frazier, Rebecca S. ; Fuchs, Heather ; Gable, Philip ; Galak, Jeff ; Galliani, Elisa Maria ; Gampa, Anup ; Garcia, Sara ; Gazarian, Douglas ; Gilbert, Elizabeth ; Giner-Sorolla, Roger ; Glöckner, Andreas ; Göllner, Lars ; Goh, Jin X. ; Goldberg, Rebecca ; Goodbourn, Patrick T. ; Gordon-McKeon, Shauna ; Gorges, Bryan ; Gorges, Jessie ; Goss, Justin ; Graham, Jesse ; Grange, James A. ; Gray, Jeremy ; Hartgerink, Chris ; Hartshorne, Joshua ; Hasselman, Fred ; Hayes, Timothy ; Heikensten, Emma ; Henninger, Felix ; Hodsoll, John ; Holubar, Taylor ; Hoogendoorn, Gea ; Humphries, Denise J. ; Hung, Cathy O. -Y. ; Immelman, Nathali ; Irsik, Vanessa C. ; Jahn, Georg ; Jaekel, Frank ; Jekel, Marc ; Johannesson, Magnus ; Johnson, Larissa G. ; Johnson, David J. ; Johnson, Kate M. ; Johnston, William J. ; Jonas, Kai ; Joy-Gaba, Jennifer A. ; Kappes, Heather Barry ; Kelso, Kim ; Kidwell, Mallory C. ; Kim, Seung Kyung ; Kirkhart, Matthew ; Kleinberg, Bennett ; Knezevic, Goran ; Kolorz, Franziska Maria ; Kossakowski, Jolanda J. ; Krause, Robert Wilhelm ; Krijnen, Job ; Kuhlmann, Tim ; Kunkels, Yoram K. ; Kyc, Megan M. ; Lai, Calvin K. ; Laique, Aamir ; Lakens, Daniel ; Lane, Kristin A. ; Lassetter, Bethany ; Lazarevic, Ljiljana B. ; LeBel, Etienne P. ; Lee, Key Jung ; Lee, Minha ; Lemm, Kristi ; Levitan, Carmel A. ; Lewis, Melissa ; Lin, Lin ; Lin, Stephanie ; Lippold, Matthias ; Loureiro, Darren ; Luteijn, Ilse ; Mackinnon, Sean ; Mainard, Heather N. ; Marigold, Denise C. ; Martin, Daniel P. ; Martinez, Tylar ; Masicampo, E. J. ; Matacotta, Josh ; Mathur, Maya ; May, Michael ; Mechin, Nicole ; Mehta, Pranjal ; Meixner, Johannes ; Melinger, Alissa ; Miller, Jeremy K. ; Miller, Mallorie ; Moore, Katherine ; Möschl, Marcus ; Motyl, Matt ; Müller, Stephanie M. ; Munafo, Marcus ; Neijenhuijs, Koen I. ; Nervi, Taylor ; Nicolas, Gandalf ; Nilsonne, Gustav ; Nosek, Brian A. ; Nuijten, Michele B. ; Olsson, Catherine ; Osborne, Colleen ; Ostkamp, Lutz ; Pavel, Misha ; Penton-Voak, Ian S. ; Perna, Olivia ; Pernet, Cyril ; Perugini, Marco ; Pipitone, R. Nathan ; Pitts, Michael ; Plessow, Franziska ; Prenoveau, Jason M. ; Rahal, Rima-Maria ; Ratliff, Kate A. ; Reinhard, David ; Renkewitz, Frank ; Ricker, Ashley A. ; Rigney, Anastasia ; Rivers, Andrew M. ; Roebke, Mark ; Rutchick, Abraham M. ; Ryan, Robert S. ; Sahin, Onur ; Saide, Anondah ; Sandstrom, Gillian M. ; Santos, David ; Saxe, Rebecca ; Schlegelmilch, Rene ; Schmidt, Kathleen ; Scholz, Sabine ; Seibel, Larissa ; Selterman, Dylan Faulkner ; Shaki, Samuel ; Simpson, William B. ; Sinclair, H. Colleen ; Skorinko, Jeanine L. M. ; Slowik, Agnieszka ; Snyder, Joel S. ; Soderberg, Courtney ; Sonnleitner, Carina ; Spencer, Nick ; Spies, Jeffrey R. ; Steegen, Sara ; Stieger, Stefan ; Strohminger, Nina ; Sullivan, Gavin B. ; Talhelm, Thomas ; Tapia, Megan ; te Dorsthorst, Anniek ; Thomae, Manuela ; Thomas, Sarah L. ; Tio, Pia ; Traets, Frits ; Tsang, Steve ; Tuerlinckx, Francis ; Turchan, Paul ; Valasek, Milan ; Van Aert, Robbie ; van Assen, Marcel ; van Bork, Riet ; van de Ven, Mathijs ; van den Bergh, Don ; van der Hulst, Marije ; van Dooren, Roel ; van Doorn, Johnny ; van Renswoude, Daan R. ; van Rijn, Hedderik ; Vanpaemel, Wolf ; Echeverria, Alejandro Vasquez ; Vazquez, Melissa ; Velez, Natalia ; Vermue, Marieke ; Verschoor, Mark ; Vianello, Michelangelo ; Voracek, Martin ; Vuu, Gina ; Wagenmakers, Eric-Jan ; Weerdmeester, Joanneke ; Welsh, Ashlee ; Westgate, Erin C. ; Wissink, Joeri ; Wood, Michael ; Woods, Andy ; Wright, Emily ; Wu, Sining ; Zeelenberg, Marcel ; Zuni, Kellylynn
Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
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