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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.
Brodeur, Abel ; Mikola, Derek ; Cook, Nikolai ; Brailey, Thomas ; Briggs, Ryan ; Gendre, Alexandra de ; Dupraz, Yannick ; Fiala, Lenka ; Gabani, Jacopo ; Gauriot, Romain ; Haddad, Joanne ; Lima, Goncalo ; Ankel-Peters, Jörg ; Dreber, Anna ; Campbell, Douglas ; Kattan, Lamis ; Fages, Diego Marino ; Mierisch, Fabian ; Sun, Pu ; Wright, Taylor ; Connolly, Marie ; Hoces de la Guardia, Fernando ; Johannesson, Magnus ; Miguel, Edward ; Vilhuber, Lars ; Abarca, Alejandro ; Acharya, Mahesh ; Adjisse, Sossou Simplice ; Akhtar, Ahwaz ; Lizardi, Eduardo Alberto Ramirez ; Albrecht, Sabina ; Andersen, Synve Nygaard ; Andlib, Zubaria ; Arrora, Falak ; Ash, Thomas ; Bacher, Etienne ; Bachler, Sebastian ; Bacon, Félix ; Bagues, Manuel ; Balogh, Timea ; Batmanov, Alisher ; Barschkett, Mara ; Basdil, B. Kaan ; Dower, Jaromneda ; Castek, Ondrej ; Caviglia-Harris, Jill ; Strand, Gabriella Chauca ; Chen, Shi ; Chzhen, Asya ; Chung, Jong ; Collins, Jason ; Coppock, Alexander ; Cordeau, Hugo ; Couillard, Ben ; Crechet, Jonathan ; Crippa, Lorenzo ; Cui, Jeanne ; Czymara, Christian ; Daarstad, Haley ; Dao, Danh Chi ; Dao, Dong ; Schmandt, Marco David ; Linde, Astrid de ; Melo, Lucas De ; Deer, Lachlan ; Vera, Micole De ; Dimitrova, Velichka ; Dollbaum, Jan Fabian ; Dollbaum, Jan Matti ; Donnelly, Michael ; Huynh, Luu Duc Toan ; Dumbalska, Tsvetomira ; Duncan, Jamie ; Duong, Kiet Tuan ; Duprey, Thibaut ; Dworschak, Christoph ; Ellingsrud, Sigmund ; Elminejad, Ali ; Eissa, Yasmine ; Erhart, Andrea ; Etingin-Frati, Giulian ; Fatemi-Pour, Elaheh ; Federice, Alexa ; Feld, Jan ; Fenig, Guidon ; Firouzjaeiangalougah, Mojtaba ; Fleisje, Erlend ; Fortier-Chouinard, Alexandre ; Engel, Julia Francesca ; Fries, Tilman ; Fortier, Reid ; Fréchet, Nadjim ; Galipeau, Thomas ; Gallegos, Sebastián ; Gangji, Areez ; Gao, Xiaoying ; Garnache, Cloé ; Gáspár, Attila ; Gavrilova, Evelina ; Ghosh, Arijit ; Gibney, Garreth ; Gibson, Grant ; Godager, Geir ; Goff, Leonard ; Gong, Da ; González, Javier ; Gretton, Jeremy ; Griffa, Cristina ; Grigoryeva, Idaliya ; Grtting, Maja ; Guntermann, Eric ; Guo, Jiaqi ; Gugushvili, Alexi ; Habibnia, Hooman ; Häffner, Sonja ; Hall, Jonathan D. ; Hammar, Olle ; Kordt, Amund Hanson ; Hashimoto, Barry ; Hartley, Jonathan S. ; Hausladen, Carina I. ; Havránek, Tomáš ; Hazen, Jacob ; He, Harry ; Hepplewhite, Matthew ; Herrera-Rodriguez, Mario ; Heuer, Felix ; Heyes, Anthony ; Ho, Anson T. Y. ; Holmes, Jonathan ; Holzknecht, Armando ; Hsu, Yu-Hsiang Dexter ; Hu, Shiang-Hung ; Huang, Yu-Shiuan ; Huebener, Mathias ; Huber, Christoph ; Huynh, Kim P. ; Irsova, Zuzana ; Isler, Ozan ; Jakobsson, Niklas ; Frith, Michael James ; Jananji, Raphaël ; Jayalath, Tharaka A. ; Jetter, Michael ; John, Jenny ; Forshaw, Rachel Joy ; Juan, Felipe ; Kadriu, Valon ; Karim, Sunny ; Kelly, Edmund ; Dang, Duy Khanh Hoang ; Khushboo, Tazia ; Kim, Jin ; Kjellsson, Gustav ; Kjelsrud, Anders ; Kotsadam, Andreas ; Korpershoek, Jori ; Krashinsky, Lewis ; Kundu, Suranjana ; Kustov, Alexander ; Lalayev, Nurlan ; Langlois, Audrée ; Laufer, Jill ; Lee-Whiting, Blake ; Leibing, Andreas ; Lenz, Gabriel ; Levin, Joel ; Li, Peng ; Li, Tongzhe ; Lin, Yuchen ; Listo, Ariel ; Liu, Dan ; Lu, Xuewen ; Lukmanova, Elvina ; Luscombe, Alex ; Lusher, Lester R. ; Lyu, Ke ; Ma, Hai ; Mäder, Nicolas ; Makate, Clifton ; Malmberg, Alice ; Maitra, Adit ; Mandas, Marco ; Marcus, Jan ; Margaryan, Shushanik ; Márk, Lili ; Martignano, Andres ; Marsh, Abigail ; Masetto, Isabella ; McCanny, Anthony ; McManus, Emma ; McWay, Ryan ; Metson, Lennard ; Kinge, Jonas Minet ; Mishra, Sumit ; Mohnen, Myra ; Möller, Jakob ; Montambeault, Rosalie ; Montpetit, Sébastien ; Morin, Louis-Philippe ; Morris, Todd ; Moser, Scott ; Motoki, Fabio ; Muehlenbachs, Lucija ; Musulan, Andreea ; Musumeci, Marco ; Nabin, Munirul ; Nchare, Karim ; Neubauer, Florian ; Nguyen, Quan M. P. ; Nguyen, Tuan ; Nguyen-Tien, Viet ; Niazi, Ali ; Nikolaishvili, Giorgi ; Nordstrom, Ardyn ; Nü, Patrick ; Odermatt, Angela ; Olson, Matt ; ien, Henning ; Ölkers, Tim ; Vert, Miquel Oliver i. ; Oral, Emre ; Oswald, Christian ; Ousman, Ali ; Özak, Ömer ; Pandey, Shubham ; Pavlov, Alexandre ; Pelli, Martino ; Penheiro, Romeo ; Park, RyuGyung ; Martel, Eva Pérez ; Petrovičová, Tereza ; Phan, Linh ; Prettyman, Alexa ; Procházka, Jakub ; Putri, Aqila ; Quandt, Julian ; Qiu, Kangyu ; Nguyen, Loan Quynh Thi ; Rahman, Andaleeb ; Rea, Carson H. ; Reiremo, Adam ; Renée, Laëtitia ; Richardson, Joseph ; Rivers, Nicholas ; Rodrigues, Bruno ; Roelofs, William ; Roemer, Tobias ; Rogeberg, Ole ; Rose, Julian ; Roskos-Ewoldsen, Andrew ; Rosmer, Paul ; Sabada, Barbara ; Saberian, Soodeh ; Salamanca, Nicolas ; Sator, Georg ; Sawyer, Antoine ; Scates, Daniel ; Schlüter, Elmar ; Sells, Cameron ; Sen, Sharmi ; Sethi, Ritika ; Shcherbiak, Anna ; Sogaolu, Moyosore ; Soosalu, Matt ; Srensen, Erik ; Sovani, Manali ; Spencer, Noah ; Staubli, Stefan ; Stans, Renske ; Stewart, Anya ; Stips, Felix ; Stockley, Kieran ; Strobel, Stephenson ; Struby, Ethan ; Tang, John ; Tanrisever, Idil ; Yang, Thomas Tao ; Tastan, Ipek ; Tatić, Dejan ; Tatlow, Benjamin ; Seuyong, Féraud Tchuisseu ; Thériault, Rémi ; Thivierge, Vincent ; Tian, Wenjie ; Toma, Filip-Mihai ; Totarelli, Maddalena ; Tran, Van-Anh ; Truong, Hung ; Tsoy, Nikita ; Tuzcuoglu, Kerem ; Ubfal, Diego ; Villalobos, Laura ; Walterskirchen, Julian ; Wang, Joseph Taoyi ; Wattal, Vasudha ; Webb, Matthew D. ; Weber, Bryan ; Weisser, Reinhard ; Weng, Wei-Chien ; Westheide, Christian ; White, Kimberly ; Winter, Jacob ; Wochner, Timo ; Woerman, Matt ; Wong, Jared ; Woodard, Ritchie ; Wroński, Marcin ; Yazbeck, Myra ; Yang, Gustav Chung ; Yap, Luther ; Yassin, Kareman ; Ye, Hao ; Yoon, Jin Young ; Yurris, Chris ; Zahra, Tahreen ; Zaneva, Mirela ; Zayat, Aline ; Zhang, Jonathan ; Zhao, Ziwei ; Yaolang, Zhong
This study pushes our understanding of research reliability by reproducing and replicating claims from 110 papers in leading economic and political science journals. The analysis involves computational reproducibility checks and robustness assessments. It reveals several patterns. First, we uncover a high rate of fully computationally reproducible results (over 85%). Second, excluding minor issues like missing packages or broken pathways, we uncover coding errors for about 25% of studies, with some studies containing multiple errors. Third, we test the robustness of the results to 5,511 re-analyses. We find a robustness reproducibility of about 70%. Robustness reproducibility rates are relatively higher for re-analyses that introduce new data and lower for re-analyses that change the sample or the definition of the dependent variable. Fourth, 52% of re-analysis effect size estimates are smaller than the original published estimates and the average statistical significance of a re-analysis is 77% of the original. Lastly, we rely on six teams of researchers working independently to answer eight additional research questions on the determinants of robustness reproducibility. Most teams find a negative relationship between replicators' experience and reproducibility, while finding no relationship between reproducibility and the provision of intermediate or even raw data combined with the necessary cleaning codes.
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.
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.
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.
Pagel, Jörn ; Anderson, Barbara J. ; Cramer, Wolfgang ; Fox, Richard ; Jeltsch, Florian ; Roy, David B. ; Thomas, Chris D. ; Schurr, Frank Martin
2. We present a hierarchical model that integrates observations from multiple sources to estimate spatio-temporal abundance trends. The model links annual population densities on a spatial grid to both long-term count data and to opportunistic occurrence records from a citizen science programme. Specific observation models for both data types explicitly account for differences in data structure and quality.
3. We test this novel method in a virtual study with simulated data and apply it to the estimation of abundance dynamics across the range of a butterfly species (Pyronia tithonus) in Great Britain between 1985 and 2004. The application to simulated and real data demonstrates how the hierarchical model structure accommodates various sources of uncertainty which occur at different stages of the link between observational data and the modelled abundance, thereby it accounts for these uncertainties in the inference of abundance variations.
4. We show that by using hierarchical observation models that integrate different types of commonly available data sources, we can improve the estimates of variation in species abundances across space and time. This will improve our ability to detect regional trends and can also enhance the empirical basis for understanding range dynamics.
Pablo, Herbert ; Richardson, Noel D. ; Moffat, Anthony F. J. ; Corcoran, Michael ; Shenar, Tomer ; Benvenuto, Omar ; Fuller, Jim ; Naze, Yael ; Hoffman, Jennifer L. ; Miroshnichenko, Anatoly ; Apellaniz, Jesus Maiz ; Evans, Nancy ; Eversberg, Thomas ; Gayley, Ken ; Gull, Ted ; Hamaguchi, Kenji ; Hamann, Wolf-Rainer ; Henrichs, Huib ; Hole, Tabetha ; Ignace, Richard ; Iping, Rosina ; Lauer, Jennifer ; Leutenegger, Maurice ; Lomax, Jamie ; Nichols, Joy ; Oskinova, Lidia M. ; Owocki, Stan ; Pollock, Andy ; Russell, Christopher M. P. ; Waldron, Wayne ; Buil, Christian ; Garrel, Thierry ; Graham, Keith ; Heathcote, Bernard ; Lemoult, Thierry ; Li, Dong ; Mauclaire, Benjamin ; Potter, Mike ; Ribeiro, Jose ; Matthews, Jaymie ; Cameron, Chris ; Guenther, David ; Kuschnig, Rainer ; Rowe, Jason ; Rucinski, Slavek ; Sasselov, Dimitar ; Weiss, Werner
We report on both high-precision photometry from the Microvariability and Oscillations of Stars (MOST) space telescope and ground-based spectroscopy of the triple system delta Ori A, consisting of a binary O9.5II+early-B (Aa1 and Aa2) with P = 5.7 days, and a more distant tertiary (O9 IV P > 400 years). This data was collected in concert with X-ray spectroscopy from the Chandra X-ray Observatory. Thanks to continuous coverage for three weeks, the MOST light curve reveals clear eclipses between Aa1 and Aa2 for the first time in non-phased data. From the spectroscopy, we have a well-constrained radial velocity (RV) curve of Aa1. While we are unable to recover RV variations of the secondary star, we are able to constrain several fundamental parameters of this system and determine an approximate mass of the primary using apsidal motion. We also detected second order modulations at 12 separate frequencies with spacings indicative of tidally influenced oscillations. These spacings have never been seen in a massive binary, making this system one of only a handful of such binaries that show evidence for tidally induced pulsations.
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