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Year of publication
Language
- English (43)
Is part of the Bibliography
- yes (43)
Keywords
- Auger electron spectroscopy (3)
- photochemistry (3)
- photofragmentation (3)
- ultrafast dynamics (3)
- Auger–Meitner (2)
- Coster–Kronig (2)
- DATM (2)
- FLASH (2)
- NEXAFS (2)
- PCLake (2)
Institute
The AlpArray seismic network
(2018)
Hetenyi, Gyorgy ; Molinari, Irene ; Clinton, John ; Bokelmann, Gotz ; Bondar, Istvan ; Crawford, Wayne C. ; Dessa, Jean-Xavier ; Doubre, Cecile ; Friederich, Wolfgang ; Fuchs, Florian ; Giardini, Domenico ; Graczer, Zoltan ; Handy, Mark R. ; Herak, Marijan ; Jia, Yan ; Kissling, Edi ; Kopp, Heidrun ; Korn, Michael ; Margheriti, Lucia ; Meier, Thomas ; Mucciarelli, Marco ; Paul, Anne ; Pesaresi, Damiano ; Piromallo, Claudia ; Plenefisch, Thomas ; Plomerova, Jaroslava ; Ritter, Joachim ; Rumpker, Georg ; Sipka, Vesna ; Spallarossa, Daniele ; Thomas, Christine ; Tilmann, Frederik ; Wassermann, Joachim ; Weber, Michael ; Weber, Zoltan ; Wesztergom, Viktor ; Zivcic, Mladen ; Abreu, Rafael ; Allegretti, Ivo ; Apoloner, Maria-Theresia ; Aubert, Coralie ; Besancon, Simon ; de Berc, Maxime Bes ; Brunel, Didier ; Capello, Marco ; Carman, Martina ; Cavaliere, Adriano ; Cheze, Jerome ; Chiarabba, Claudio ; Cougoulat, Glenn ; Cristiano, Luigia ; Czifra, Tibor ; Danesi, Stefania ; Daniel, Romuald ; Dannowski, Anke ; Dasovic, Iva ; Deschamps, Anne ; Egdorf, Sven ; Fiket, Tomislav ; Fischer, Kasper ; Funke, Sigward ; Govoni, Aladino ; Groschl, Gidera ; Heimers, Stefan ; Heit, Ben ; Herak, Davorka ; Huber, Johann ; Jaric, Dejan ; Jedlicka, Petr ; Jund, Helene ; Klingen, Stefan ; Klotz, Bernhard ; Kolinsky, Petr ; Kotek, Josef ; Kuhne, Lothar ; Kuk, Kreso ; Lange, Dietrich ; Loos, Jurgen ; Lovati, Sara ; Malengros, Deny ; Maron, Christophe ; Martin, Xavier ; Massa, Marco ; Mazzarini, Francesco ; Metral, Laurent ; Moretti, Milena ; Munzarova, Helena ; Nardi, Anna ; Pahor, Jurij ; Pequegnat, Catherine ; Petersen, Florian ; Piccinini, Davide ; Pondrelli, Silvia ; Prevolnik, Snjezan ; Racine, Roman ; Regnier, Marc ; Reiss, Miriam ; Salimbeni, Simone ; Santulin, Marco ; Scherer, Werner ; Schippkus, Sven ; Schulte-Kortnack, Detlef ; Solarino, Stefano ; Spieker, Kathrin ; Stipcevic, Josip ; Strollo, Angelo ; Sule, Balint ; Szanyi, Gyongyver ; Szucs, Eszter ; Thorwart, Martin ; Ueding, Stefan ; Vallocchia, Massimiliano ; Vecsey, Ludek ; Voigt, Rene ; Weidle, Christian ; Weyland, Gauthier ; Wiemer, Stefan ; Wolf, Felix ; Wolyniec, David ; Zieke, Thomas
The AlpArray programme is a multinational, European consortium to advance our understanding of orogenesis and its relationship to mantle dynamics, plate reorganizations, surface processes and seismic hazard in the Alps-Apennines-Carpathians-Dinarides orogenic system. The AlpArray Seismic Network has been deployed with contributions from 36 institutions from 11 countries to map physical properties of the lithosphere and asthenosphere in 3D and thus to obtain new, high-resolution geophysical images of structures from the surface down to the base of the mantle transition zone. With over 600 broadband stations operated for 2 years, this seismic experiment is one of the largest simultaneously operated seismological networks in the academic domain, employing hexagonal coverage with station spacing at less than 52 km. This dense and regularly spaced experiment is made possible by the coordinated coeval deployment of temporary stations from numerous national pools, including ocean-bottom seismometers, which were funded by different national agencies. They combine with permanent networks, which also required the cooperation of many different operators. Together these stations ultimately fill coverage gaps. Following a short overview of previous large-scale seismological experiments in the Alpine region, we here present the goals, construction, deployment, characteristics and data management of the AlpArray Seismic Network, which will provide data that is expected to be unprecedented in quality to image the complex Alpine mountains at depth.
Maier, Philipp ; Wolf, Jürgen ; Keilig, Thomas ; Krabbe, Alfred ; Duffard, Rene ; Ortiz, Jose-Luis ; Klinkner, Sabine ; Lengowski, Michael ; Müller, Thomas ; Lockowandt, Christian ; Krockstedt, Christian ; Kappelmann, Norbert ; Stelzer, Beate ; Werner, Klaus ; Geier, Stephan ; Kalkuhl, Christoph ; Rauch, Thomas ; Schanz, Thomas ; Barnstedt, Jürgen ; Conti, Lauro ; Hanke, Lars
This paper presents the concept of a community-accessible stratospheric balloon-based observatory that is currently under preparation by a consortium of European research institutes and industry. We present the technical motivation, science case, instrumentation, and a two-stage image stabilization approach of the 0.5-m UV/visible platform. In addition, we briefly describe the novel mid-sized stabilized balloon gondola under design to carry telescopes in the 0.5 to 0.6 m range as well as the currently considered flight option for this platform. Secondly, we outline the scientific and technical motivation for a large balloon-based FIR telescope and the ESBO DS approach towards such an infrastructure.
Taal, H. Rob ; St Pourcain, Beate ; Thiering, Elisabeth ; Das, Shikta ; Mook-Kanamori, Dennis O. ; Warrington, Nicole M. ; Kaakinen, Marika ; Kreiner-Moller, Eskil ; Bradfield, Jonathan P. ; Freathy, Rachel M. ; Geller, Frank ; Guxens, Monica ; Cousminer, Diana L. ; Kerkhof, Marjan ; Timpson, Nicholas J. ; Ikram, M. Arfan ; Beilin, Lawrence J. ; Bonnelykke, Klaus ; Buxton, Jessica L. ; Charoen, Pimphen ; Chawes, Bo Lund Krogsgaard ; Eriksson, Johan ; Evans, David M. ; Hofman, Albert ; Kemp, John P. ; Kim, Cecilia E. ; Klopp, Norman ; Lahti, Jari ; Lye, Stephen J. ; McMahon, George ; Mentch, Frank D. ; Mueller-Nurasyid, Martina ; O'Reilly, Paul F. ; Prokopenko, Inga ; Rivadeneira, Fernando ; Steegers, Eric A. P. ; Sunyer, Jordi ; Tiesler, Carla ; Yaghootkar, Hanieh ; Breteler, Monique M. B. ; Debette, Stephanie ; Fornage, Myriam ; Gudnason, Vilmundur ; Launer, Lenore J. ; van der Lugt, Aad ; Mosley, Thomas H. ; Seshadri, Sudha ; Smith, Albert V. ; Vernooij, Meike W. ; Blakemore, Alexandra I. F. ; Chiavacci, Rosetta M. ; Feenstra, Bjarke ; Fernandez-Banet, Julio ; Grant, Struan F. A. ; Hartikainen, Anna-Liisa ; van der Heijden, Albert J. ; Iniguez, Carmen ; Lathrop, Mark ; McArdle, Wendy L. ; Molgaard, Anne ; Newnham, John P. ; Palmer, Lyle J. ; Palotie, Aarno ; Pouta, Annneli ; Ring, Susan M. ; Sovio, Ulla ; Standl, Marie ; Uitterlinden, Andre G. ; Wichmann, H-Erich ; Vissing, Nadja Hawwa ; DeCarli, Charles ; van Duijn, Cornelia M. ; McCarthy, Mark I. ; Koppelman, Gerard H. ; Estivill, Xavier ; Hattersley, Andrew T. ; Melbye, Mads ; Bisgaard, Hans ; Pennell, Craig E. ; Widen, Elisabeth ; Hakonarson, Hakon ; Smith, George Davey ; Heinrich, Joachim ; Jarvelin, Marjo-Riitta ; Jaddoe, Vincent W. V. ; Adair, Linda S. ; Ang, Wei ; Atalay, Mustafa ; van Beijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Bradfield, Jonathan P. ; Charoen, Pimphen ; Coin, Lachlan ; Cousminer, Diana L. ; Das, Shikta ; Davis, Oliver S. P. ; Elliott, Paul ; Evans, David M. ; Feenstra, Bjarke ; Flexeder, Claudia ; Frayling, Tim ; Freathy, Rachel M. ; Gaillard, Romy ; Geller, Frank ; Groen-Blokhuis, Maria ; Goh, Liang-Kee ; Guxens, Monica ; Haworth, Claire M. A. ; Hadley, Dexter ; Hebebrand, Johannes ; Hinney, Anke ; Hirschhorn, Joel N. ; Holloway, John W. ; Holst, Claus ; Hottenga, Jouke Jan ; Horikoshi, Momoko ; Huikari, Ville ; Hypponen, Elina ; Iniguez, Carmen ; Kaakinen, Marika ; Kilpelainen, Tuomas O. ; Kirin, Mirna ; Kowgier, Matthew ; Lakka, Hanna-Maaria ; Lange, Leslie A. ; Lawlor, Debbie A. ; Lehtimaki, Terho ; Lewin, Alex ; Lindgren, Cecilia ; Lindi, Virpi ; Maggi, Reedik ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Mook-Kanamori, Dennis O. ; Murray, Jeffrey C. ; Nivard, Michel ; Nohr, Ellen Aagaard ; Ntalla, Ioanna ; Oken, Emily ; O'Reilly, Paul F. ; Palmer, Lyle J. ; Panoutsopoulou, Kalliope ; Pararajasingham, Jennifer ; Prokopenko, Inga ; Rodriguez, Alina ; Salem, Rany M. ; Sebert, Sylvain ; Siitonen, Niina ; Sovio, Ulla ; St Pourcain, Beate ; Strachan, David P. ; Sunyer, Jordi ; Taal, H. Rob ; Teo, Yik-Ying ; Thiering, Elisabeth ; Tiesler, Carla ; Uitterlinden, Andre G. ; Valcarcel, Beatriz ; Warrington, Nicole M. ; White, Scott ; Willemsen, Gonneke ; Yaghootkar, Hanieh ; Zeggini, Eleftheria ; Boomsma, Dorret I. ; Cooper, Cyrus ; Estivill, Xavier ; Gillman, Matthew ; Grant, Struan F. A. ; Hakonarson, Hakon ; Hattersley, Andrew T. ; Heinrich, Joachim ; Hocher, Berthold ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; Lakka, Timo A. ; McCarthy, Mark I. ; Melbye, Mads ; Mohlke, Karen L. ; Dedoussis, George V. ; Ong, Ken K. ; Pearson, Ewan R. ; Pennell, Craig E. ; Price, Thomas S. ; Power, Chris ; Raitakari, Olli T. ; Saw, Seang-Mei ; Scherag, Andre ; Simell, Olli ; Sorensen, Thorkild I. A. ; Timpson, Nicholas J. ; Widen, Elisabeth ; Wilson, James F. ; Ang, Wei ; van Beijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Bradfield, Jonathan P. ; Charoen, Pimphen ; Coin, Lachlan ; Cousminer, Diana L. ; Das, Shikta ; Elliott, Paul ; Evans, David M. ; Frayling, Tim ; Freathy, Rachel M. ; Gaillard, Romy ; Groen-Blokhuis, Maria ; Guxens, Monica ; Hadley, Dexter ; Hottenga, Jouke Jan ; Huikari, Ville ; Hypponen, Elina ; Kaakinen, Marika ; Kowgier, Matthew ; Lawlor, Debbie A. ; Lewin, Alex ; Lindgren, Cecilia ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Mook-Kanamori, Dennis O. ; Nivard, Michel ; O'Reilly, Paul F. ; Palmer, Lyle J. ; Prokopenko, Inga ; Rodriguez, Alina ; Sebert, Sylvain ; Sovio, Ulla ; St Pourcain, Beate ; Standl, Marie ; Strachan, David P. ; Sunyer, Jordi ; Taal, H. Rob ; Thiering, Elisabeth ; Tiesler, Carla ; Uitterlinden, Andre G. ; Valcarcel, Beatriz ; Warrington, Nicole M. ; White, Scott ; Willemsen, Gonneke ; Yaghootkar, Hanieh ; Boomsma, Dorret I. ; Estivill, Xavier ; Grant, Struan F. A. ; Hakonarson, Hakon ; Hattersley, Andrew T. ; Heinrich, Joachim ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; McCarthy, Mark I. ; Pennell, Craig E. ; Power, Chris ; Timpson, Nicholas J. ; Widen, Elisabeth ; Ikram, M. Arfan ; Fornage, Myriam ; Smith, Albert V. ; Seshadri, Sudha ; Schmidt, Reinhold ; Debette, Stephanie ; Vrooman, Henri A. ; Sigurdsson, Sigurdur ; Ropele, Stefan ; Coker, Laura H. ; Longstreth, W. T. ; Niessen, Wiro J. ; DeStefano, Anita L. ; Beiser, Alexa ; Zijdenbos, Alex P. ; Struchalin, Maksim ; Jack, Clifford R. ; Nalls, Mike A. ; Au, Rhoda ; Hofman, Albert ; Gudnason, Haukur ; van der Lugt, Aad ; Harris, Tamara B. ; Meeks, William M. ; Vernooij, Meike W. ; van Buchem, Mark A. ; Catellier, Diane ; Gudnason, Vilmundur ; Windham, B. Gwen ; Wolf, Philip A. ; van Duijn, Cornelia M. ; Mosley, Thomas H. ; Schmidt, Helena ; Launer, Lenore J. ; Breteler, Monique M. B. ; DeCarli, Charles
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
Granacher, Urs ; Mühlbauer, Thomas ; Bridenbaugh, Stephanie A. ; Wolf, Madeleine ; Roth, Ralf ; Gschwind, Yves ; Wolf, Irene ; Mata, Rui ; Kressig, Reto W.
Background: Deficits in static and particularly dynamic postural control and force production have frequently been associated with an increased risk of falling in older adults. Objective: The objectives of this study were to investigate the effects of salsa dancing on measures of static/dynamic postural control and leg extensor power in seniors. Methods: Twenty-eight healthy older adults were randomly assigned to an intervention group (INT, n = 14, age 71.6 +/- 5.3 years) to conduct an 8-week progressive salsa dancing programme or a control group (CON, n = 14, age 68.9 +/- 4.7 years). Static postural control was measured during one-legged stance on a balance platform and dynamic postural control was obtained while walking on an instrumented walkway. Leg extensor power was assessed during a countermovement jump on a force plate. Results: Programme compliance was excellent with participants of the INT group completing 92.5% of the dancing sessions. A tendency towards an improvement in the selected measures of static postural control was observed in the INT group as compared to the CON group. Significant group X test interactions were found for stride velocity, length and time. Post hoc analyses revealed significant increases in stride velocity and length, and concomitant decreases in stride time. However, salsa dancing did not have significant effects on various measures of gait variability and leg extensor power. Conclusion: Salsa proved to be a safe and feasible exercise programme for older adults accompanied with a high adherence rate. Age-related deficits in measures of static and particularly dynamic postural control can be mitigated by salsa dancing in older adults. High physical activity and fitness/mobility levels of our participants could be responsible for the nonsignificant findings in gait variability and leg extensor power.
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.
Ikram, M. Arfan ; Fornage, Myriam ; Smith, Albert V. ; Seshadri, Sudha ; Schmidt, Reinhold ; Debette, Stephanie ; Vrooman, Henri A. ; Sigurdsson, Sigurdur ; Ropele, Stefan ; Taal, H. Rob ; Mook-Kanamori, Dennis O. ; Coker, Laura H. ; Longstreth, W. T. ; Niessen, Wiro J. ; DeStefano, Anita L. ; Beiser, Alexa ; Zijdenbos, Alex P. ; Struchalin, Maksim ; Jack, Clifford R. ; Rivadeneira, Fernando ; Uitterlinden, Andre G. ; Knopman, David S. ; Hartikainen, Anna-Liisa ; Pennell, Craig E. ; Thiering, Elisabeth ; Steegers, Eric A. P. ; Hakonarson, Hakon ; Heinrich, Joachim ; Palmer, Lyle J. ; Jarvelin, Marjo-Riitta ; McCarthy, Mark I. ; Grant, Struan F. A. ; St Pourcain, Beate ; Timpson, Nicholas J. ; Smith, George Davey ; Sovio, Ulla ; Nalls, Mike A. ; Au, Rhoda ; Hofman, Albert ; Gudnason, Haukur ; van der Lugt, Aad ; Harris, Tamara B. ; Meeks, William M. ; Vernooij, Meike W. ; van Buchem, Mark A. ; Catellier, Diane ; Jaddoe, Vincent W. V. ; Gudnason, Vilmundur ; Windham, B. Gwen ; Wolf, Philip A. ; van Duijn, Cornelia M. ; Mosley, Thomas H. ; Schmidt, Helena ; Launer, Lenore J. ; Breteler, Monique M. B. ; DeCarli, Charles ; Adair, Linda S. ; Ang, Wei ; Atalay, Mustafa ; vanBeijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Coin, Lachlan ; Davis, Oliver S. P. ; Elliott, Paul ; Flexeder, Claudia ; Frayling, Tim ; Gaillard, Romy ; Groen-Blokhuis, Maria ; Goh, Liang-Kee ; Haworth, Claire M. A. ; Hadley, Dexter ; Hebebrand, Johannes ; Hinney, Anke ; Hirschhorn, Joel N. ; Holloway, John W. ; Holst, Claus ; Hottenga, Jouke Jan ; Horikoshi, Momoko ; Huikari, Ville ; Hypponen, Elina ; Kilpelainen, Tuomas O. ; Kirin, Mirna ; Kowgier, Matthew ; Lakka, Hanna-Maaria ; Lange, Leslie A. ; Lawlor, Debbie A. ; Lehtimaki, Terho ; Lewin, Alex ; Lindgren, Cecilia ; Lindi, Virpi ; Maggi, Reedik ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Murray, Jeffrey C. ; Nivard, Michel ; Nohr, Ellen Aagaard ; Ntalla, Ioanna ; Oken, Emily ; Panoutsopoulou, Kalliope ; Pararajasingham, Jennifer ; Rodriguez, Alina ; Salem, Rany M. ; Sebert, Sylvain ; Siitonen, Niina ; Strachan, David P. ; Teo, Yik-Ying ; Valcarcel, Beatriz ; Willemsen, Gonneke ; Zeggini, Eleftheria ; Boomsma, Dorret I. ; Cooper, Cyrus ; Gillman, Matthew ; Hocher, Berthold ; Lakka, Timo A. ; Mohlke, Karen L. ; Dedoussis, George V. ; Ong, Ken K. ; Pearson, Ewan R. ; Price, Thomas S. ; Power, Chris ; Raitakari, Olli T. ; Saw, Seang-Mei ; Scherag, Andre ; Simell, Olli ; Sorensen, Thorkild I. A. ; Wilson, James F.
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
Reimold, Wolf Uwe ; Fischer, Luise ; Müller, Jan ; Kenkmann, Thomas ; Schmitt, Ralf-Thomas ; Altenberger, Uwe ; Kowitz, Astrid
Pseudotachylitic breccia (PTB) in the form of cm-wide melt breccia veinlets locally occurs on the exposed central uplift of the 380Ma Siljan impact structure. The host rock to the PTBs is the so-called Jarna granite of quartz monzonitic to syenodioritic composition. The nearly 603m long BH-5 drill core from Hattberg, near the centre of the Siljan central uplift, contains numerous veins and pods of PTB. In particular, two major zones of 60m combined width contain extensive PTB network breccias (30% actual melt breccia component), with individual melt breccia occurrences up to >1m in length. Core logging and petrographic and geochemical analysis of the core have been performed, and the data are interpreted to suggest the following. (1) The impact event caused low to moderate (at essentially <20GPa) shock deformation in the host rock and in clasts of this lithology within the PTB. (2) Macroscopic deformation of the basement mainly comprises fracturing, with only localised cataclasis. (3) No evidence for shock melting (i.e. compression/decompression melting early in the cratering process) could be observed. (4) Optical and scanning electron microscopy showed that dark PTB contains a definite melt component. (5) Shearing has significantly affected this part of the central uplift, but its effects are limited to very short displacements and likely did not result in extensive melting. (6) A frictional heating component upon melt generation can, however, not be excluded, as many PTB samples contain clasts of a mafic (gabbroic) component, although only in one place along the entire core, a 1.2cm-wide section through such material in direct contact to host rock was observed. Consequently, we suggest that, upon uplift in the central part of the impact structure, considerable melt volumes were generated locally, especially in areas that had been affected by extensive cataclasis and where grain size comminution favoured melt formation. Rapid decompression related to central uplift formation is the preferred process for the generation of the PTB melt breccias.
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.
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.