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Niemi, Mari K. ; Karjalainen, Juha ; Liao, Rachel G. ; Neale, Benjamin M. ; Daly, Mark ; Ganna, Andrea ; Pathak, Gita A. ; Andrews, Shea J. ; Kanai, Masahiro ; Veerapen, Kumar ; Fernandez-Cadenas, Israel ; Schulte, Eva C. ; Striano, Pasquale ; Marttila, Minttu ; Minica, Camelia ; Marouli, Eirini ; Karim, Mohd Anisul ; Wendt, Frank R. ; Savage, Jeanne ; Sloofman, Laura ; Butler-Laporte, Guillaume ; Kim, Han-Na ; Kanoni, Stavroula ; Okada, Yukinori ; Byun, Jinyoung ; Han, Younghun ; Uddin, Mohammed Jashim ; Smith, George Davey ; Willer, Cristen J. ; Buxbaum, Joseph D. ; Mehtonen, Juha ; Finucane, Hilary ; Cordioli, Mattia ; Martin, Alicia R. ; Zhou, Wei ; Pasaniuc, Bogdan ; Julienne, Hanna ; Aschard, Hugues ; Shi, Huwenbo ; Yengo, Loic ; Polimanti, Renato ; Ghoussaini, Maya ; Schwartzentruber, Jeremy ; Dunham, Ian ; Chwialkowska, Karolina ; Francescatto, Margherita ; Trankiem, Amy ; Balaconis, Mary K. ; Davis, Lea ; Lee, Sulggi ; Priest, James ; Renieri, Alessandra ; Sankaran, Vijay G. ; van Heel, David ; Deelen, Patrick ; Richards, J. Brent ; Nakanishi, Tomoko ; Biesecker, Les ; Kerchberger, V. Eric ; Baillie, J. Kenneth ; Mari, Francesca ; Bernasconi, Anna ; Baillie, Stefano Ceri ; Canakoglu, Arif ; Wolford, Brooke ; Faucon, Annika ; Dutta, Atanu Kumar ; Schurmann, Claudia ; Harry, Emi ; Birney, Ewan ; Nguyen, Huy ; Nasir, Jamal ; Kaunisto, Mari ; Solomonson, Matthew ; Dueker, Nicole ; Vadgama, Nirmal ; Limou, Sophie ; Rahmouni, Souad ; Mbarek, Hamdi ; Darwish, Dima ; Uddin, Md Mesbah ; Albertos, Raquel ; Pérez-Tur, Jordi ; Li, Ruolin ; Folkersen, Lasse ; Moltke, Ida ; Koelling, Nils ; Teumer, Alexander ; Kousathanas, Athanasios ; Utrilla, Alicia ; Verdugo, Ricardo A. ; Zárate, Ruth ; Medina-Gómez, Carolina ; Gómez-Cabrero, David ; Carnero-Montoro, Elena ; Cadilla, Carmen L. ; Moreno-Estrada, Andrés ; Garmendia, Adriana ; Moya, Leire ; Sedaghati-Khayat, Bahar ; Boua, Palwendé Romuald ; Favé, Marie-Julie ; Francioli, Laurent ; Lemaçon, Audrey ; Migeotte, Isabelle ; Patel, Sanjay ; Varnai, Reka ; Szentpeteri, Jozsef L. ; Sipeky, Csilla ; Colombo, Francesca ; von Hohenstaufen, Kathrin ; Lio, Pietro ; Vallerga, Costanza ; Wang, Qingbo ; Tanigawa, Yosuke ; Im, Hogune ; Han, Chulho ; Song, Han ; Lim, Jiwoo ; Lee, Younhe ; Kim, Sugyeong ; Im, Sangyoon ; Atanasovska, Biljana ; Ahmad, Hajar Fauzan ; Boer, Cindy ; Jansen, Philip ; Franke, Lude ; Kaja, Elżbieta ; Pasko, Dorota ; Kennis-Szilagyi, Ingrid ; Kornilov, Sergey A. ; Prijatelj, Vid ; Prokić, Ivana ; Sivanadhan, Ilangkumaran ; Perumal, Sarala ; Esmaeeli, Sahar ; Pearson, Nathaniel M. ; Auton, Adam ; Shelton, Janie F. ; Shastri, Anjali J. ; Filshtein-Sonmez, Teresa ; Coker, Daniella ; Symons, Antony ; Esparza-Gordillo, Jorge ; Aslibekyan, Stella ; O’Connell, Jared ; Ye, Chelsea ; Weldon, Catherine H. ; Perera, Minoli ; O’Leary, Kevin ; Tuck, Matthew ; O’Brien, Travis ; Meltzer, David ; O’Donnell, Peter ; Nutescu, Edith ; Yang, Guang ; Alarcon, Cristina ; Herrmann, Stefanie ; Mazurek, Sophia ; Banagan, Jeff ; Hamidi, Zacharia ; Barbour, April ; Raffat, Noora ; Moreno, Diana ; Friedman, Paula ; Ferwerda, Bart ; van de Beek, Diederik ; Brouwer, Matthijs C. ; Vlaar, Alexander P. J. ; Wiersinga, W. Joost ; Posthuma, Danielle ; Tissink, Elleke ; Koos Zwinderman, A. H. ; Uffelmann, Emil ; van Agtmael, Michiel ; Algera, Anne Geke ; van Baarle, Frank ; Bax, Diane ; Beudel, Martijn ; Jan Bogaard, Harm ; Bomers, Marije ; Bonta, Peter I. ; Bos, Lieuwe ; Botta, Michela ; de Brabander, Justin ; de Bree, Godelieve ; de Bruin, Sanne ; Bugiani, Marianna ; Bulle, Esther ; Chouchane, Osoul ; Cloherty, Alex ; Dongelmans, Dave ; Elbers, Paul ; Fleuren, Lucas ; Geerlings, Suzanne ; Geerts, Bart ; Geijtenbeek, Theo ; Girbes, Armand ; Goorhuis, Bram ; Grobusch, Martin P. ; Hafkamp, Florianne ; Hagens, Laura ; Hamann, Jorg ; Harris, Vanessa ; Hemke, Robert ; Hermans, Sabine M. ; Heunks, Leo ; Hollmann, Markus ; Horn, Janneke ; Hovius, Joppe W. ; de Jong, Menno D. ; Koning, Rutger ; van Mourik, Niels ; Nellen, Jeannine ; Nossent, Esther J. ; Paulus, Frederique ; Peters, Edgar ; van der Poll, Tom ; Preckel, Bennedikt ; Prins, Jan M. ; Raasveld, Jorinde ; Reijnders, Tom ; Schinkel, Michiel ; Schultz, Marcus J. ; Schuurman, Alex ; Sigaloff, Kim ; Smit, Marry ; Stijnis, Cornelis S. ; Stilma, Willemke ; Teunissen, Charlotte ; Thoral, Patrick ; Tsonas, Anissa ; van der Valk, Marc ; Veelo, Denise ; de Vries, Heder ; van Vugt, Michèle ; Wouters, Dorien ; Minnaar, René P. ; Kromhout, Adrie ; van Uffelen, Kees W. J. ; Wolterman, Ruud A. ; Roberts, Genevieve ; Park, Danny ; Ball, Catherine A. ; Coignet, Marie ; McCurdy, Shannon ; Knight, Spencer ; Partha, Raghavendran ; Rhead, Brooke ; Zhang, Miao ; Berkowitz, Nathan ; Gaddis, Michael ; Noto, Keith ; Ruiz, Luong ; Pavlovic, Milos ; Hong, Eurie L. ; Rand, Kristin ; Girshick, Ahna ; Guturu, Harendra ; Baltzell, Asher Haug ; Rahmouni, Souad ; Guntz, Julien ; Beguin, Yves ; Pigazzini, Sara ; Nkambule, Lindokuhle ; Bouysran, Youssef ; Busson, Adeline ; Peyrassol, Xavier ; Wilkin, Françoise ; Pichon, Bruno ; Smits, Guillaume ; Vandernoot, Isabelle ; Goffard, Jean-Christophe ; Georges, Michel ; Moutschen, Michel ; Misset, Benoit ; Darcis, Gilles ; Guiot, Julien ; Jadot, Laurent ; Azarzar, Samira ; Dellot, Patricia ; Gofflot, Stéphanie ; Claassen, Sabine ; Bertrand, Axelle ; Parzibut, Gilles ; Clarinval, Mathilde ; Moermans, Catherine ; Malaise, Olivier ; El Kandoussi, Kamilia ; Thonon, Raphaël ; Huynen, Pascale ; Mesdagh, Alyssia ; Melo, Sofia ; Jacques, Nicolas ; Di Valentin, Emmanuel ; Giroule, François ; Collignon, Alice ; Radermecker, Coraline ; Lebrun, Marielle ; Perée, Hélène ; Latour, Samuel ; Barada, Olivia ; Sanchez, Judit ; Josse, Claire ; Boujemla, Bouchra ; Meunier, Margot ; Mariavelle, Emeline ; Anania, Sandy ; Gazon, Hélène ; Juszczak, Danusia ; Fadeur, Marjorie ; Camby, Séverine ; Meuris, Christelle ; Thys, Marie ; Jacques, Jessica ; Henket, Monique ; Léonard, Philippe ; Frippiat, Frederic ; Giot, Jean-Baptiste ; Sauvage, Anne-Sophie ; Von Frenckell, Christian ; Mni, Myriam ; Wéry, Marie ; Staderoli, Alicia ; Belhaj, Yasmine ; Lambermont, Bernard ; Morrison, David R. ; Mooser, Vincent ; Forgetta, Vincenzo ; Li, Rui ; Ghosh, Biswarup ; Laurent, Laetitia ; Belisle, Alexandre ; Henry, Danielle ; Abdullah, Tala ; Adeleye, Olumide ; Mamlouk, Noor ; Kimchi, Nofar ; Afrasiabi, Zaman ; Rezk, Nardin ; Vulesevic, Branka ; Bouab, Meriem ; Guzman, Charlotte ; Petitjean, Louis ; Tselios, Chris ; Xue, Xiaoqing ; Afilalo, Jonathan ; Afilalo, Marc ; Oliveira, Maureen ; Brenner, Bluma ; Brassard, Nathalie ; Durand, Madeleine ; Schurr, Erwin ; Lepage, Pierre ; Ragoussis, Jiannis ; Auld, Daniel ; Chassé, Michaël ; Kaufmann, Daniel E. ; Lathrop, G. Mark ; Adra, Darin ; Davis, Lea K. ; Cox, Nancy J. ; Below, Jennifer E. ; Sealock, Julia M. ; Faucon, Annika B. ; Shuey, Megan M. ; Polikowsky, Hannah G. ; Petty, Lauren E. ; Shaw, Douglas M. ; Chen, Hung-Hsin ; Zhu, Wanying ; Ludwig, Kerstin U. ; Schröder, Julia ; Maj, Carlo ; Rolker, Selina ; Nöthen, Markus M. ; Fazaal, Julia ; Keitel, Verena ; Jensen, Björn-Erik Ole ; Feldt, Torsten ; Kurth, Ingo ; Marx, Nikolaus ; Dreher, Michael ; Pink, Isabell ; Cornberg, Markus ; Illig, Thomas ; Lehmann, Clara ; Schommers, Philipp ; Augustin, Max ; Rybniker, Jan ; Knopp, Lisa ; Eggermann, Thomas ; Volland, Sonja ; Altmüller, Janine ; Berger, Marc M. ; Brenner, Thorsten ; Hinney, Anke ; Witzke, Oliver ; Bals, Robert ; Herr, Christian ; Ludwig, Nicole ; Walter, Jörn ; Fuchsberger, Christian ; Pattaro, Cristian ; De Grandi, Alessandro ; Pramstaller, Peter ; Emmert, David ; Melotti, Roberto ; Foco, Luisa ; Mascalzoni, Deborah ; Gögele, Martin ; Domingues, Francisco ; Hicks, Andrew ; Gignoux, Christopher R. ; Wicks, Stephen J. ; Crooks, Kristy ; Barnes, Kathleen C. ; Daya, Michelle ; Shortt, Jonathan ; Rafaels, Nicholas ; Chavan, Sameer ; Goldstein, David B. ; Kiryluk, Krzysztof ; Sengupta, Soumitra ; Chung, Wendy ; Reilly, Muredach P. ; Khan, Atlas ; Wang, Chen ; Povysil, Gundula ; Bhardwaj, Nitin ; Gharavi, Ali G. ; Ionita-Laza, Iuliana ; Shang, Ning ; O’Byrne, Sheila M. ; Nandakumar, Renu ; Menon, Amritha ; So, Yat S. ; Hod, Eldad ; Pendrick, Danielle ; Kim, Han-Na ; Park, Soo-Kyung ; Kim, Hyung-Lae ; Kang, Chang Kyung ; Lee, Hyo-Jung ; Song, Kyoung-Ho ; Jae Yoon, Kyung ; Paik, Nam-Jong ; Seok, Woojin ; Yoon, Heejun ; Joo, Eun-Jeong ; Chang, Yoosoo ; Ryu, Seungho ; Park, Wan Beom ; Su Park, Jeong ; Un Park, Kyoung ; Ham, Sin Young ; Jung, Jongtak ; Kim, Eu Suk ; Kim, Hong Bin ; Ellinghaus, David ; Degenhardt, Frauke ; Cáceres, Mario ; Juzenas, Simonas ; Lenz, Tobias L. ; Albillos, Agustín ; Julià, Antonio ; Heidecker, Bettina ; Garcia, Federico ; Kurth, Florian ; Tran, Florian ; Hanses, Frank ; Zoller, Heinz ; Holter, Jan C. ; Fernández, Javier ; Sander, Leif Erik ; Rosenstiel, Philip ; Koehler, Philipp ; de Cid, Rafael ; Asselta, Rosanna ; Schreiber, Stefan ; Hehr, Ute ; Prati, Daniele ; Baselli, Guido ; Valenti, Luca ; Bujanda, Luis ; Banales, Jesus M. ; Duga, Stefano ; D’Amato, Mauro ; Romero-Gómez, Manuel ; Buti, Maria ; Invernizzi, Pietro ; Franke, Andre ; Hov, Johannes R. ; Karlsen, Tom H. ; Folseraas, Trine ; Maya-Miles, Douglas ; Teles, Ana ; Azuure, Clinton ; Wacker, Eike Matthias ; Uellendahl-Werth, Florian ; ElAbd, Hesham ; Arora, Jatin ; Lerga-Jaso, Jon ; Wienbrandt, Lars ; Rühlemann, Malte Christoph ; Wendorff, Mareike ; Vadla, May Sissel ; Lenning, Ole Bernt ; Özer, Onur ; Myhre, Ronny ; Raychaudhuri, Soumya ; Tanck, Anja ; Gassner, Christoph ; Hemmrich-Stanisak, Georg ; Kässens, Jan ; Figuera Basso, Maria E. ; Schulzky, Martin ; Wittig, Michael ; Braun, Nicole ; Wesse, Tanja ; Albrecht, Wolfgang ; Yi, Xiaoli ; Ortiz, Aaron Blandino ; Chercoles, Adolfo Garrido ; Ruiz, Agustín ; Mantovani, Alberto ; Holten, Aleksander Rygh ; Mayer, Alena ; Cherubini, Alessandro ; Protti, Alessandro ; Aghemo, Alessio ; Gerussi, Alessio ; Ramirez, Alfredo ; Braun, Alice ; Barreira, Ana ; Lleo, Ana ; Kildal, Anders Benjamin ; Glück, Andreas ; Nolla, Anna Carreras ; Latiano, Anna ; Dyrhol-Riise, Anne Ma ; Muscatello, Antonio ; Voza, Antonio ; Rando-Segura, Ariadna ; Solier, Aurora ; Karina, Banasik ; Cortes, Beatriz ; Mateos, Beatriz ; Nafria-Jimenez, Beatriz ; Schaefer, Benedikt ; Bellinghausen, Carla ; Ferrando, Carlos ; Quereda, Carmen ; Skurk, Carsten ; Thibeault, Charlotte ; Spinner, Christoph D. ; Lange, Christoph ; Hu, Cinzia ; Cappadona, Claudio ; Bianco, Cristiana ; Sancho, Cristina ; Lihaug Hoff, Dag Arne ; Galimberti, Daniela ; Jiménez, David ; Pestaña, David ; Toapanta, David ; Azzolini, Elena ; Scarpini, Elio ; Helbig, Elisa T. ; Urrechaga, Eloisa ; Paraboschi, Elvezia Maria ; Pontali, Emanuele ; Reverter, Enric ; Navas, Enrique ; Arana, Eunate ; Sánchez, Félix García ; Ceriotti, Ferruccio ; Malvestiti, Francesco ; Mesonero, Francisco ; Pezzoli, Gianni ; Lamorte, Giuseppe ; Neb, Holger ; My, Ilaria ; Hernández, Isabel ; de Rojas, Itziar ; Galván-Femenia, Iván ; Heyckendorf, Jan ; Rybniker, Jan ; Badia, Joan Ramon ; Schneider, Jochen ; Goikoetxea, Josune ; Kraft, Julia ; Müller, Karl Erik ; Gaede, Karoline I. ; Garcia-Etxebarria, Koldo ; Tonby, Kristian ; Heggelund, Lars ; Izquierdo-Sanchez, Laura ; Sumoy, Lauro ; Lippert, Lena J. ; Terranova, Leonardo ; Garbarino, Lucia ; Téllez, Luis ; Roade, Luisa ; Ostadreza, Mahnoosh ; Intxausti, Maider ; Kogevinas, Manolis ; Gutiérrez-Stampa, María A. ; Vehreschild, Maria J. G. T. ; Marquié, Marta ; Castoldi, Massimo ; Cecconi, Maurizio ; Boada, Mercè ; Seilmaier, Michael J. ; Mazzocco, Michela ; Rodríguez-Gandía, Miguel ; Ayo, Natale Imaz ; Blay, Natalia ; Martínez, Nilda ; Cornely, Oliver A. ; Palmieri, Orazio ; Tentorio, Paolo ; Rodrigues, Pedro M. ; España, Pedro P. ; Hoffmann, Per ; Bacher, Petra ; Suwalski, Phillip ; de Pablo, Raúl ; Nieto, Rosa ; Badalamenti, Salvatore ; Ciesek, Sandra ; Bombace, Sara ; Wilfling, Sibylle ; Brunak, Søren ; Heilmann-Heimbach, Stefanie ; Ripke, Stephan ; Bahmer, Thomas ; Landmesser, Ulf ; Protzer, Ulrike ; Rimoldi, Valeria ; Skogen, Vegard ; Andrade, Victor ; Moreno, Victor ; Poller, Wolfgang ; Farre, Xavier ; Wang, Xiaomin ; Khodamoradi, Yascha ; Karadeniz, Zehra ; de Salazar, Adolfo ; Palom, Adriana ; Garcia-Fernandez, Alba-Estela ; Blanco-Grau, Albert ; Zanella, Alberto ; Bandera, Alessandra ; Nebel, Almut ; Biondi, Andrea ; Caballero-Garralda, Andrea ; Gori, Andrea ; Lind, Andreas ; Fracanzani, Anna Ludovica ; Peschuck, Anna ; Pesenti, Antonio ; de la Horra, Carmen ; Milani, Chiara ; Paccapelo, Cinzia ; Angelini, Claudio ; Cea, Cristina ; Muñiz-Diaz, Eduardo ; Sandoval, Elena ; Calderón, Enrique J. ; Solligård, Erik ; Aziz, Fátima ; Martinelli-Boneschi, Filippo ; Peyvandi, Flora ; Blasi, Francesco ; Medrano, Francisco J. ; Rodriguez-Frias, Francisco ; Müller, Fredrik ; Grasselli, Giacomo ; Costantino, Giorgio ; Cardamone, Giulia ; Foti, Giuseppe ; Matullo, Giuseppe ; Kurihara, Hayato ; Afset, Jan Egil ; Damås, Jan Kristian ; Ampuero, Javier ; Martín, Javier ; Erdmann, Jeanette ; Bergan, Jonas ; Goerg, Siegfried ; Ferrusquía-Acosta, Jose ; Quero, Jose Hernández ; Delgado, Juan ; Guerrero, Juan M. ; Risnes, Kari ; Bettini, Laura Rachele ; Moreira, Leticia ; Gustad, Lise Tuset ; Santoro, Luigi ; Scudeller, Luigia ; Riveiro-Barciela, Mar ; Schaefer, Marco ; Carrabba, Maria ; Valsecchi, Maria G. ; Hernandez-Tejero, María ; Acosta-Herrera, Marialbert ; D’Angiò, Mariella ; Baldini, Marina ; Cazzaniga, Marina ; Ciccarelli, Michele ; Bocciolone, Monica ; Miozzo, Monica ; Chueca, Natalia ; Montano, Nicola ; Faverio, Paola ; Preatoni, Paoletta ; Bonfanti, Paolo ; Omodei, Paolo ; Castro, Pedro ; Ferrer, Ricard ; Gualtierotti, Roberta ; Gallego-Durán, Rocío ; Morilla, Rubén ; Haider, Sammra ; Marsal, Sara ; Aneli, Serena ; Pelusi, Serena ; Bosari, Silvano ; Aliberti, Stefano ; Dudman, Susanne ; Zheng, Tenghao ; Pumarola, Tomas ; Cejudo, Trinidad Gonzalez ; Monzani, Valter ; Friaza, Vicente ; Peter, Wolfgang ; Dopazo, Ximo ; Duga, Stefano ; May, Sandra ; Grimsrud, Marit M. ; Gudbjartsson, Daniel F. ; Stefansson, Kari ; Sulem, Patrick ; Sveinbjornsson, Gardar ; Melsted, Pall ; Norddahl, Gudmundur ; Swerford Moore, Kristjan Helgi ; Thorsteinsdottir, Unnur ; Holm, Hilma ; Alarcón-Riquelme, Marta E. ; Bernardo, David ; Martínez-Bueno, Manuel ; Rello, Silvia Rojo ; Magi, Reedik ; Milani, Lili ; Metspalu, Andres ; Laisk, Triin ; Läll, Kristi ; Lepamets, Maarja ; Esko, Tõnu ; Reimann, Ene ; Naaber, Paul ; Laane, Edward ; Pesukova, Jaana ; Peterson, Pärt ; Kisand, Kai ; Tabri, Jekaterina ; Allos, Raili ; Hensen, Kati ; Starkopf, Joel ; Ringmets, Inge ; Tamm, Anu ; Kallaste, Anne ; Alavere, Helene ; Metsalu, Kristjan ; Puusepp, Mairo ; Kristiansson, Kati ; Koskelainen, Sami ; Perola, Markus ; Donner, Kati ; Kivinen, Katja ; Palotie, Aarno ; Palotie, Aarno ; Rivolta, Carlo ; Bochud, Pierre-Yves ; Bibert, Stéphanie ; Boillat, Noémie ; Nussle, Semira Gonseth ; Albrich, Werner ; Quinodoz, Mathieu ; Kamdar, Dhryata ; Suh, Noémie ; Neofytos, Dionysios ; Erard, Véronique ; Voide, Cathy ; Bochud, P. Y. ; Rivolta, C. ; Bibert, S. ; Quinodoz, M. ; Kamdar, D. ; Neofytos, D. ; Erard, V. ; Voide, C. ; Friolet, R. ; Vollenweider, P. ; Pagani, J. L. ; Oddo, M. ; zu Bentrup, F. Meyer ; Conen, A. ; Clerc, O. ; Marchetti, O. ; Guillet, A. ; Guyat-Jacques, C. ; Foucras, S. ; Rime, M. ; Chassot, J. ; Jaquet, M. ; Viollet, R. Merlet ; Lannepoudenx, Y. ; Portopena, L. ; Desgranges, F. ; Filippidis, P. ; Guéry, B. ; Haefliger, D. ; Kampouri, E. E. ; Manuel, O. ; Munting, A. ; Papadimitriou-Olivgeris, M. ; Regina, J. ; Rochat-Stettler, L. ; Suttels, V. ; Tadini, E. ; Tschopp, J. ; Van Singer, M. ; Viala, B. ; Boillat-Blanco, N. ; Brahier, T. ; Hügli, O. ; Meuwly, J. Y. ; Pantet, O. ; Nussle, S. Gonseth ; Bochud, M. ; D’Acremont, V. ; Younes, S. Estoppey ; Albrich, W. C. ; Suh, N. ; Cerny, A. ; O’Mahony, L. ; von Mering, C. ; Bochud, P. Y. ; Frischknecht, M. ; Kleger, G.-R. ; Filipovic, M. ; Kahlert, C. R. ; Wozniak, H. ; Negro, T. Rochat ; Pugin, J. ; Bouras, K. ; Knapp, C. ; Egger, T. ; Perret, A. ; Montillier, P. ; di Bartolomeo, C. ; Barda, B. ; de Cid, Rafael ; Carreras, Anna ; Moreno, Victor ; Galván-Femenía, Iván ; Blay, Natalia ; Farré, Xavier ; Sumoy, Lauro ; Cortés, Beatriz ; Mercader, Josep Maria ; Guindo-Martinez, Marta ; Torrents, David ; Garcia-Aymerich, Judith ; Castaño-Vinyals, Gemma ; Dobaño, Carlota ; Gori, Marco ; Renieri, Alessandra ; Mondelli, Mario Umberto ; Castelli, Francesco ; Vaghi, Massimo ; Rusconi, Stefano ; Montagnani, Francesca ; Bargagli, Elena ; Franchi, Federico ; Mazzei, Maria Antonietta ; Cantarini, Luca ; Tacconi, Danilo ; Feri, Marco ; Scala, Raffaele ; Spargi, Genni ; Nencioni, Cesira ; Bandini, Maria ; Caldarelli, Gian Piero ; Spagnesi, Maurizio ; Canaccini, Anna ; Ognibene, Agostino ; D’Arminio Monforte, Antonella ; Girardis, Massimo ; Antinori, Andrea ; Francisci, Daniela ; Schiaroli, Elisabetta ; Scotton, Pier Giorgio ; Panese, Sandro ; Scaggiante, Renzo ; Monica, Matteo Della ; Capasso, Mario ; Fiorentino, Giuseppe ; Castori, Marco ; Aucella, Filippo ; Di Biagio, Antonio ; Masucci, Luca ; Valente, Serafina ; Mandalà, Marco ; Zucchi, Patrizia ; Giannattasio, Ferdinando ; Coviello, Domenico A. ; Mussini, Cristina ; Bosio, Giancarlo ; Tavecchia, Luisa ; Crotti, Lia ; Rizzi, Marco ; La Rovere, Maria Teresa ; Sarzi-Braga, Simona ; Bussotti, Maurizio ; Ravaglia, Sabrina ; Artuso, Rosangela ; Perrella, Antonio ; Romani, Davide ; Bergomi, Paola ; Catena, Emanuele ; Vincenti, Antonella ; Ferri, Claudio ; Grassi, Davide ; Pessina, Gloria ; Tumbarello, Mario ; Di Pietro, Massimo ; Sabrina, Ravaglia ; Luchi, Sauro ; Barbieri, Chiara ; Acquilini, Donatella ; Andreucci, Elena ; Paciosi, Francesco ; Segala, Francesco Vladimiro ; Tiseo, Giusy ; Falcone, Marco ; Lista, Mirjam ; Poscente, Monica ; De Vivo, Oreste ; Petrocelli, Paola ; Guarnaccia, Alessandra ; Baroni, Silvia ; Perticaroli, Valentina ; Furini, Simone ; Dei, Simona ; Benetti, Elisa ; Picchiotti, Nicola ; Sanarico, Maurizio ; Ceri, Stefano ; Pinoli, Pietro ; Raimondi, Francesco ; Biscarini, Filippo ; Stella, Alessandra ; Bergomi, Mattia ; Zguro, Kristina ; Capitani, Katia ; Tanfoni, Marco ; Fallerini, Chiara ; Daga, Sergio ; Baldassarri, Margherita ; Fava, Francesca ; Frullanti, Elisa ; Valentino, Floriana ; Doddato, Gabriella ; Giliberti, Annarita ; Tita, Rossella ; Amitrano, Sara ; Bruttini, Mirella ; Croci, Susanna ; Meloni, Ilaria ; Mencarelli, Maria Antonietta ; Lo Rizzo, Caterina ; Pinto, Anna Maria ; Beligni, Giada ; Tommasi, Andrea ; Di Sarno, Laura ; Palmieri, Maria ; Carriero, Miriam Lucia ; Alaverdian, Diana ; Iuso, Nicola ; Inchingolo, Gabriele ; Busani, Stefano ; Bruno, Raffaele ; Vecchia, Marco ; Belli, Mary Ann ; Mantovani, Stefania ; Ludovisi, Serena ; Quiros-Roldan, Eugenia ; Antoni, Melania Degli ; Zanella, Isabella ; Siano, Matteo ; Emiliozzi, Arianna ; Fabbiani, Massimiliano ; Rossetti, Barbara ; Zanelli, Giacomo ; Bergantini, Laura ; D’Alessandro, Miriana ; Cameli, Paolo ; Bennet, David ; Anedda, Federico ; Marcantonio, Simona ; Scolletta, Sabino ; Guerrini, Susanna ; Conticini, Edoardo ; Frediani, Bruno ; Spertilli, Chiara ; Donati, Alice ; Guidelli, Luca ; Corridi, Marta ; Croci, Leonardo ; Piacentini, Paolo ; Desanctis, Elena ; Cappelli, Silvia ; Verzuri, Agnese ; Anemoli, Valentina ; Pancrazi, Alessandro ; Lorubbio, Maria ; Merlini, Esther ; Miraglia, Federica Gaia ; Venturelli, Sophie ; Cossarizza, Andrea ; Vergori, Alessandra ; Gabrieli, Arianna ; Riva, Agostino ; Paciosi, Francesco ; Andretta, Francesca ; Gatti, Francesca ; Parisi, Saverio Giuseppe ; Baratti, Stefano ; Piscopo, Carmelo ; Russo, Roberta ; Andolfo, Immacolata ; Iolascon, Achille ; Carella, Massimo ; Merla, Giuseppe ; Squeo, Gabriella Maria ; Raggi, Pamela ; Marciano, Carmen ; Perna, Rita ; Bassetti, Matteo ; Sanguinetti, Maurizio ; Giorli, Alessia ; Salerni, Lorenzo ; Parravicini, Pierpaolo ; Menatti, Elisabetta ; Trotta, Tullio ; Coiro, Gabriella ; Lena, Fabio ; Martinelli, Enrico ; Mancarella, Sandro ; Gabbi, Chiara ; Maggiolo, Franco ; Ripamonti, Diego ; Bachetti, Tiziana ; Suardi, Claudia ; Parati, Gianfranco ; Bottà, Giordano ; Di Domenico, Paolo ; Rancan, Ilaria ; Bianchi, Francesco ; Colombo, Riccardo ; van Heel, David A. ; Hunt, Karen A. ; Trembath, Richard C. ; Huang, Qin Qin ; Martin, Hilary C. ; Mason, Dan ; Trivedi, Bhavi ; Wright, John ; Finer, Sarah ; Griffiths, Christopher J. ; Akhtar, Shaheen ; Anwar, Mohammad ; Arciero, Elena ; Ashraf, Samina ; Breen, Gerome ; Chung, Raymond ; Curtis, Charles J. ; Chowdhury, Maharun ; Colligan, Grainne ; Deloukas, Panos ; Durham, Ceri ; Finer, Sarah ; Griffiths, Chris ; Huang, Qin Qin ; Hurles, Matt ; Hunt, Karen A. ; Hussain, Shapna ; Islam, Kamrul ; Khan, Ahsan ; Khan, Amara ; Lavery, Cath ; Lee, Sang Hyuck ; Lerner, Robin ; MacArthur, Daniel ; MacLaughlin, Bev ; Martin, Hilary ; Mason, Dan ; Miah, Shefa ; Newman, Bill ; Safa, Nishat ; Tahmasebi, Farah ; Trembath, Richard C. ; Trivedi, Bhavi ; van Heel, David A. ; Wright, John ; Smith, Albert V. ; Boughton, Andrew P. ; Li, Kevin W. ; LeFaive, Jonathon ; Annis, Aubrey ; Jannes, Cinthia E. ; Krieger, Jose E. ; Pereira, Alexandre C. ; Velho, Mariliza ; Marques, Emanuelle ; Lima, Isabella Ramos ; Tada, Mauricio Teruo ; Valino, Karina ; McCarthy, Mark ; Rosenberger, Carrie ; Lee, Jong Eun ; Chang, Diana ; Hammer, Christian ; Hunkapiller, Julie ; Mahajan, Anubha ; Pendergrass, Sarah ; Sucheston-Campbell, Lara ; Yaspan, Brian ; Lee, Hyun Soo ; Shin, Eunsoon ; Jang, Hye Yoon ; Kim, Sunmie ; Kym, Sungmin ; Kim, Yeon-Sook ; Jeong, Hyeongseok ; Kwon, Ki Tae ; Kim, Shin-Woo ; Kim, Jin Yong ; Jang, Young Rock ; Kim, Hyun ah ; Lee, Ji Yeon ; Lee, Jeong Eun ; Lee, Shinwon ; Choe, Kang-Won ; Kang, Yu Min ; Jee, Sun Ha ; Jung, Keum Ji ; Parikh, Victoria ; Ashley, Euan ; Wheeler, Matthew ; Rivas, Manuel ; Bustamante, Carlos ; Pinksy, Benjamin ; Febbo, Phillip ; Farh, Kyle ; Schroth, Gary P. ; deSouza, Francis ; Dalton, Karen ; Christle, Jeff ; Deboever, Christopher ; Szalma, Sándor ; Tanigawa, Yosuke ; Rubinacci, Simone ; Delaneau, Olivier ; Gorzynski, John ; de Jong, Hannah ; Sutton, Shirley ; Youlton, Nathan ; Joshi, Ruchi ; Jimenez-Morales, David ; Hughes, Christopher ; Amar, David ; Ioannidis, Alex ; Hershman, Steve ; Kirillova, Anna ; Seo, Kinya ; Huang, Yong ; Shoura, Massa ; Hammond, Nathan ; Watson, Nathaniel ; Raja, Archana ; Huang, ChunHong ; Sahoo, Malaya ; Wang, Hannah ; Zhen, Jimmy ; Rakitko, Alexander ; Ilinsky, Valery ; Yermakovich, Danat ; Popov, Iaroslav ; Chernitsov, Alexander ; Kovalenko, Elena ; Krasnenko, Anna ; Plotnikov, Nikolay ; Stetsenko, Ivan ; Kim, Anna ; Cirulli, Elizabeth T. ; Schiabor Barrett, Kelly M. ; Bolze, Alexandre ; White, Simon ; Washington, Nicole L. ; Lu, James T. ; Riffle, Stephen ; Tanudjaja, Francisco ; Wang, Xueqing ; Ramirez, Jimmy M. ; Leonetti, Nicole ; Sandoval, Efren ; Neveux, Iva ; Dabe, Shaun ; Grzymski, Joseph J. ; Esteban Miñano, Juan Ignacio ; Aguirre, Luis A. ; López-Collazo, Eduardo ; de la Mata Pazos, Manuel ; Cerrato, Luciano ; Folkersen, Lasse ; Lozano-Rodríguez, Roberto ; Avendaño-Ortiz, José ; Arcos, Verónica Terrón ; Montalbán-Hernández, Karla Marina ; Quiroga, Jaime Valentín ; Pascual-Iglesias, Alejandro ; Maroun-Eid, Charbel ; Martín-Quirós, Alejandro ; Namkoong, Ho ; Okada, Yukinori ; Imoto, Seiya ; Katayama, Kazuhiko ; Fukunaga, Koichi ; Kitagawa, Yuko ; Sato, Toshiro ; Hasegawa, Naoki ; Kumanogoh, Atsushi ; Kimura, Akinori ; Ai, Masumi ; Tokunaga, Katsushi ; Kanai, Takanori ; Miyano, Satoru ; Ogawa, Seishi ; Edahiro, Ryuya ; Sonehara, Kyuto ; Shirai, Yuya ; Kanai, Masahiro ; Ishii, Makoto ; Kabata, Hiroki ; Masaki, Katsunori ; Kamata, Hirofumi ; Ikemura, Shinnosuke ; Chubachi, Shotaro ; Okamori, Satoshi ; Terai, Hideki ; Tanaka, Hiromu ; Morita, Atsuho ; Lee, Ho ; Asakura, Takanori ; Sasaki, Junichi ; Morisaki, Hiroshi ; Uwamino, Yoshifumi ; Nanki, Kosaku ; Mikami, Yohei ; Tomono, Kazunori ; Kato, Kazuto ; Matsuda, Fumihiko ; Takahashi, Meiko ; Hizawa, Nobuyuki ; Takeda, Yoshito ; Hirata, Haruhiko ; Shiroyama, Takayuki ; Miyawaki, Satoru ; Suzuki, Ken ; Maeda, Yuichi ; Nii, Takuro ; Noda, Yoshimi ; Niitsu, Takayuki ; Adachi, Yuichi ; Enomoto, Takatoshi ; Amiya, Saori ; Hara, Reina ; Takahashi, Kunihiko ; Anzai, Tatsuhiko ; Hasegawa, Takanori ; Ito, Satoshi ; Koike, Ryuji ; Endo, Akifumi ; Uchimura, Yuji ; Miyazaki, Yasunari ; Honda, Takayuki ; Tateishi, Tomoya ; Tohda, Shuji ; Ichimura, Naoya ; Sonobe, Kazunari ; Sassa, Chihiro ; Nakajima, Jun ; Nannya, Yasuhito ; Omae, Yosuke ; Takahashi, Kazuhisa ; Harada, Norihiro ; Hiki, Makoto ; Takagi, Haruhi ; Nakamura, Ai ; Tagaya, Etsuko ; Kawana, Masatoshi ; Arimura, Ken ; Ishiguro, Takashi ; Takayanagi, Noboru ; Isono, Taisuke ; Takaku, Yotaro ; Takano, Kenji ; Anan, Ryusuke ; Nakajima, Yukiko ; Nakano, Yasushi ; Nishio, Kazumi ; Ueda, Soichiro ; Hayashi, Reina ; Tateno, Hiroki ; Hase, Isano ; Yoshida, Shuichi ; Suzuki, Shoji ; Mitamura, Keiko ; Saito, Fumitake ; Ueda, Tetsuya ; Azuma, Masanori ; Nagasaki, Tadao ; Yasui, Yoshinori ; Hasegawa, Yoshinori ; Mutoh, Yoshikazu ; Yoshiyama, Takashi ; Shoko, Tomohisa ; Kojima, Mitsuaki ; Adachi, Tomohiro ; Ishikawa, Motonao ; Takahashi, Kenichiro ; Watanabe, Kazuyoshi ; Manabe, Tadashi ; Ito, Fumimaro ; Fukui, Takahiro ; Funatsu, Yohei ; Koh, Hidefumi ; Hirai, Yoshihiro ; Kawashima, Hidetoshi ; Narita, Atsuya ; Niwa, Kazuki ; Sekikawa, Yoshiyuki ; Saito, Fukuki ; Yoshiya, Kazuhisa ; Yoshihara, Tomoyuki ; Suzuki, Yusuke ; Nakayama, Sohei ; Masuzawa, Keita ; Nishi, Koichi ; Nishitsuji, Masaru ; Tani, Maiko ; Inoue, Takashi ; Hirano, Toshiyuki ; Kobayashi, Keigo ; Miyazawa, Naoki ; Kimura, Yasuhiro ; Sado, Reiko ; Ogura, Takashi ; Kitamura, Hideya ; Murohashi, Kota ; Nakachi, Ichiro ; Baba, Rie ; Arai, Daisuke ; Fuke, Satoshi ; Saito, Hiroshi ; Kuwahara, Naota ; Fujiwara, Akiko ; Okada, Takenori ; Baba, Tomoya ; Noda, Junya ; Mashimo, Shuko ; Yagi, Kazuma ; Shiomi, Tetsuya ; Hashiguchi, Mizuha ; Odani, Toshio ; Mochimaru, Takao ; Oyamada, Yoshitaka ; Mori, Nobuaki ; Izumi, Namiki ; Nagata, Kaoru ; Taki, Reiko ; Murakami, Koji ; Yamada, Mitsuhiro ; Sugiura, Hisatoshi ; Hayashi, Kentaro ; Shimizu, Tetsuo ; Gon, Yasuhiro ; Fujitani, Shigeki ; Tsuchida, Tomoya ; Yoshida, Toru ; Kagaya, Takashi ; Kita, Toshiyuki ; Sakagami, Satoru ; Kimizuka, Yoshifumi ; Kawana, Akihiko ; Nakamura, Yoshihiko ; Ishikura, Hiroyasu ; Takata, Tohru ; Kikuchi, Takahide ; Taniyama, Daisuke ; Nakamura, Morio ; Kodama, Nobuhiro ; Kaneyama, Yasunari ; Maeda, Shunsuke ; Nagasaki, Yoji ; Okamoto, Masaki ; Ishihara, Sayoko ; Ito, Akihiro ; Chihara, Yusuke ; Takeuchi, Mayumi ; Onoi, Keisuke ; Hashimoto, Naozumi ; Wakahara, Keiko ; Ando, Akira ; Masuda, Makoto ; Wakabayashi, Aya ; Watanabe, Hiroki ; Sageshima, Hisako ; Nakada, Taka-Aki ; Abe, Ryuzo ; Shimada, Tadanaga ; Kawamura, Kodai ; Ichikado, Kazuya ; Nishiyama, Kenta ; Yamasaki, Masaki ; Hashimoto, Satoru ; Kusaka, Yu ; Ohba, Takehiko ; Isogai, Susumu ; Takada, Minoru ; Kanda, Hidenori ; Komase, Yuko ; Sano, Fumiaki ; Asano, Koichiro ; Oguma, Tsuyoshi ; Harada, Masahiro ; Takahashi, Takeshi ; Shibusawa, Takayuki ; Abe, Shinji ; Kono, Yuta ; Togashi, Yuki ; Izumo, Takehiro ; Inomata, Minoru ; Awano, Nobuyasu ; Ogawa, Shinichi ; Ogata, Tomouki ; Ishihara, Shoichiro ; Kanehiro, Arihiko ; Ozaki, Shinji ; Fuchimoto, Yasuko ; Kitagawa, Yuichiro ; Yoshida, Shozo ; Ogura, Shinji ; Nishiyama, Kei ; Yoshida, Kousuke ; Beppu, Satoru ; Fukuyama, Satoru ; Eriguchi, Yoshihiro ; Yonekawa, Akiko ; Inoue, Yoshiaki ; Yamagata, Kunihiro ; Chiba, Shigeru ; Narumoto, Osamu ; Nagai, Hideaki ; Ooshima, Nobuharu ; Motegi, Mitsuru ; Sagara, Hironori ; Tanaka, Akihiko ; Ohta, Shin ; Shibata, Yoko ; Tanino, Yoshinori ; Sato, Yuki ; Yamada, Yuichiro ; Hashino, Takuya ; Shinoki, Masato ; Iwagoe, Hajime ; Imamura, Tomonori ; Umeda, Akira ; Shimada, Hisato ; Endo, Mayu ; Hayashi, Shinichi ; Takahashi, Mai ; Nakano, Shigefumi ; Yatomi, Masakiyo ; Maeno, Toshitaka ; Ishii, Tomoo ; Utsugi, Mitsuyoshi ; Ono, Akihiro ; Kanaoka, Kensuke ; Ihara, Shoichi ; Komuta, Kiyoshi ; Franke, Lude ; Boezen, Marike ; Claringbould, Annique ; Lopera, Esteban ; Warmerdam, Robert ; Vonk, Judith. M. ; van Blokland, Irene ; Lanting, Pauline ; Ori, Anil P. S. ; Obeidat, Ma’en ; Hernández Cordero, Ana I. ; Sin, Don D. ; Bossé, Yohan ; Joubert, Philippe ; Hao, Ke ; Nickle, David ; Timens, Wim ; van den Berge, Maarten ; Feng, Yen-Chen Anne ; Mercader, Josep ; Weiss, Scott T. ; Karlson, Elizabeth W. ; Smoller, Jordan W. ; Murphy, Shawn N. ; Meigs, James B. ; Woolley, Ann E. ; Green, Robert C. ; Perez, Emma F. ; Wolford, Brooke ; Zöllner, Sebastian ; Wang, Jiongming ; Beck, Andrew ; Sloofman, Laura G. ; Ascolillo, Steven ; Sebra, Robert P. ; Collins, Brett L. ; Levy, Tess ; Sealfon, Stuart C. ; Jordan, Daniel M. ; Thompson, Ryan C. ; Gettler, Kyle ; Chaudhary, Kumardeep ; Belbin, Gillian M. ; Preuss, Michael ; Hoggart, Clive ; Choi, Sam ; Underwood, Slayton J. ; Salib, Irene ; Britvan, Bari ; Keller, Katherine ; Tang, Lara ; Peruggia, Michael ; Hiester, Liam L. ; Niblo, Kristi ; Aksentijevich, Alexandra ; Labkowsky, Alexander ; Karp, Avrohom ; Zlatopolsky, Menachem ; Zyndorf, Marissa ; Charney, Alexander W. ; Beckmann, Noam D. ; Schadt, Eric E. ; Abul-Husn, Noura S. ; Cho, Judy H. ; Itan, Yuval ; Kenny, Eimear E. ; Loos, Ruth J. F. ; Nadkarni, Girish N. ; Do, Ron ; O’Reilly, Paul ; Huckins, Laura M. ; Ferreira, Manuel A. R. ; Abecasis, Goncalo R. ; Leader, Joseph B. ; Cantor, Michael N. ; Justice, Anne E. ; Carey, Dave J. ; Chittoor, Geetha ; Josyula, Navya Shilpa ; Kosmicki, Jack A. ; Horowitz, Julie E. ; Baras, Aris ; Gass, Matthew C. ; Yadav, Ashish ; Mirshahi, Tooraj ; Jan Hottenga, Jouke ; Bartels, Meike ; de Geus, Eco J. C. ; Nivard, Michel G. ; Verma, Anurag ; Ritchie, Marylyn D. ; Rader, Daniel ; Li, Binglan ; Verma, Shefali S. ; Lucas, Anastasia ; Bradford, Yuki ; Zara, Federico ; Salpietro, Vincenzo ; Scala, Marcello ; Iacomino, Michele ; Scudieri, Paolo ; Bocciardi, Renata ; Minetti, Carlo ; Riva, Antonella ; Vari, Maria Stella ; Rahier, Jean-François ; Giorgio, Elisa ; Carli, Diana ; Louis, Edouad ; Bulik, Cynthia M. ; Landén, Mikael ; Brusco, Alfredo ; Ferrero, Giovanni Battista ; Madia, Francesca ; Fundín, Bengt ; Ismail, Said I. ; Saad, Chadi ; Al-Sarraj, Yaser ; Badji, Radja Messai ; Al-Muftah, Wadha ; Al Thani, Asma ; Afifi, Nahla ; Klovins, Janis ; Rovite, Vita ; Rescenko, Raimonds ; Peculis, Raitis ; Ustinova, Monta ; Zeberg, Hugo ; Frithiof, Robert ; Hultström, Michael ; Lipcsey, Miklos ; Johnson, Ruth ; Geschwind, Daniel H. ; Freimer, Nelson ; Butte, Manish J. ; Geschwind, Daniel H. ; Pasaniuc, Bogdan ; Ding, Yi ; Chiu, Alec ; Chang, Timothy S. ; Boutros, Paul ; Moutsianas, Loukas ; Caulfield, Mark J. ; Scott, Richard H. ; Walker, Susan ; Stuckey, Alex ; Odhams, Christopher A. ; Rhodes, Daniel ; Fowler, Tom ; Rendon, Augusto ; Chan, Georgia ; Arumugam, Prabhu ; Karczewski, Konrad J. ; Wilson, Daniel J. ; Spencer, Chris A. ; Crook, Derrick W. ; Wyllie, David H. ; O’Connell, Anne Marie ; Atkinson, Elizabeth G. ; Kanai, Masahiro ; Tsuo, Kristin ; Baya, Nikolas ; Turley, Patrick ; Gupta, Rahul ; Walters, Raymond K. ; Palmer, Duncan S. ; Sarma, Gopal ; Solomonson, Matthew ; Cheng, Nathan ; Lu, Wenhan ; Churchhouse, Claire ; Goldstein, Jacqueline I. ; King, Daniel ; Seed, Cotton ; Daly, Mark J. ; Neale, Benjamin M. ; Bryant, Sam ; Satterstrom, F. Kyle ; Band, Gavin ; Earle, Sarah G. ; Lin, Shang-Kuan ; Arning, Nicolas ; Armstrong, Jacob ; Rudkin, Justine K. ; Callier, Shawneequa ; Bryant, Sam ; Cusick, Caroline ; Soranzo, Nicole ; Zhao, Jing Hua ; Danesh, John ; Di Angelantonio, Emanuele ; Butterworth, Adam S. ; Sun, Yan V. ; Huffman, Jennifer E. ; Cho, Kelly ; O’Donnell, Christopher J. ; Tsao, Phil ; Gaziano, J. Michael ; Peloso, Gina ; Ho, Yuk-Lam ; Mian, Michael ; Scaggiante, Federica ; Chang, Xiao ; Glessner, Joseph R. ; Hakonarson, Hakon ; McGuigan, Peter J. ; Prockter Moore, Luke Stephen ; Vizcaychipi, Marcela Paola ; Hall, Kathryn ; Campbell, Andy ; Nichol, Ailstair ; Ward, Geraldine ; Page, Valerie Joan ; Semple, Malcolm G. ; Adeniji, Kayode ; Agranoff, Daniel ; Agwuh, Ken ; Ail, Dhiraj ; Aldera, Erin L. ; Alegria, Ana ; Angus, Brian ; Ashish, Abdul ; Atkinson, Dougal ; Bari, Shahedal ; Barlow, Gavin ; Barnass, Stella ; Barrett, Nicholas ; Bassford, Christopher ; Basude, Sneha ; Baxter, David ; Beadsworth, Michael ; Bernatoniene, Jolanta ; Berridge, John ; Best, Nicola ; Bothma, Pieter ; Chadwick, David ; Brittain-Long, Robin ; Bulteel, Naomi ; Burden, Tom ; Burtenshaw, Andrew ; Caruth, Vikki ; Chambler, Duncan ; Chee, Nigel ; Child, Jenny ; Chukkambotla, Srikanth ; Clark, Tom ; Collini, Paul ; Cosgrove, Catherine ; Cupitt, Jason ; Cutino-Moguel, Maria-Teresa ; Dark, Paul ; Dawson, Chris ; Dervisevic, Samir ; Donnison, Phil ; Douthwaite, Sam ; Drummond, Andrew ; DuRand, Ingrid ; Dushianthan, Ahilanadan ; Dyer, Tristan ; Evans, Cariad ; Eziefula, Chi ; Fegan, Christopher ; Finn, Adam ; Fullerton, Duncan ; Garg, Sanjeev ; Garg, Atul ; Gkrania-Klotsas, Effrossyni ; Godden, Jo ; Goldsmith, Arthur ; Graham, Clive ; Hardy, Elaine ; Hartshorn, Stuart ; Harvey, Daniel ; Havalda, Peter ; Hawcutt, Daniel B. ; Hobrok, Maria ; Hodgson, Luke ; Hormis, Anil ; Jacobs, Michael ; Jain, Susan ; Jennings, Paul ; Kaliappan, Agilan ; Kasipandian, Vidya ; Kegg, Stephen ; Kelsey, Michael ; Kendall, Jason ; Kerrison, Caroline ; Kerslake, Ian ; Koch, Oliver ; Koduri, Gouri ; Koshy, George ; Laha, Shondipon ; Laird, Steven
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
O’Connell, Kevin S. ; Koromina, Maria ; van der Veen, Tracey ; Boltz, Toni ; David, Friederike S. ; Kay Yang, Jessica Mei ; Lin, Keng-Han ; Wang, Xin ; Coleman, Jonathan R. I. ; Mitchell, Brittany L. ; McGrouther, Caroline C. ; Rangan, Aaditya V. ; Lind, Penelope A. ; Koch, Elise ; Harder, Arvid ; Parker, Nadine ; Bendl, Jaroslav ; Adorjan, Kristina ; Agerbo, Esben ; Albani, Diego ; Alemany, Silvia ; Alliey-Rodriguez, Ney ; Als, Thomas D. ; Andlauer, Till F. M. ; Antoniou, Anastasia ; Ask, Helga ; Bass, Nicholas ; Bauer, Michael ; Beins, Eva C. ; Bigdeli, Tim B. ; Pedersen, Carsten Bøcker ; Boks, Marco P. ; Børte, Sigrid ; Bosch, Rosa ; Brum, Murielle ; Brumpton, Ben M. ; Brunkhorst-Kanaan, Nathalie ; Budde, Monika ; Bybjerg-Grauholm, Jonas ; Byerley, William ; Cabana-Domínguez, Judit ; Cairns, Murray J. ; Carpiniello, Bernardo ; Casas, Miquel ; Cervantes, Pablo ; Chatzinakos, Chris ; Chen, Hsi-Chung ; Clarence, Tereza ; Clarke, Toni-Kim ; Claus, Isabelle ; Coombes, Brandon ; Corfield, Elizabeth C. ; Cruceanu, Cristiana ; Cuellar-Barboza, Alfredo ; Czerski, Piotr M. ; Dafnas, Konstantinos ; Dale, Anders M. ; Dalkner, Nina ; Degenhardt, Franziska ; DePaulo, J. Raymond ; Djurovic, Srdjan ; Drange, Ole Kristian ; Escott-Price, Valentina ; Fanous, Ayman H. ; Fellendorf, Frederike T. ; Ferrier, I. Nicol ; Forty, Liz ; Frank, Josef ; Frei, Oleksandr ; Freimer, Nelson B. ; Fullard, John F. ; Garnham, Julie ; Gizer, Ian R. ; Gordon, Scott D. ; Gordon-Smith, Katherine ; Greenwood, Tiffany A. ; Grove, Jakob ; Guzman-Parra, José ; Ha, Tae Hyon ; Hahn, Tim ; Haraldsson, Magnus ; Hautzinger, Martin ; Havdahl, Alexandra ; Heilbronner, Urs ; Hellgren, Dennis ; Herms, Stefan ; Hickie, Ian B. ; Hoffmann, Per ; Holmans, Peter A. ; Huang, Ming-Chyi ; Ikeda, Masashi ; Jamain, Stéphane ; Johnson, Jessica S. ; Jonsson, Lina ; Kalman, Janos L. ; Kamatani, Yoichiro ; Kennedy, James L. ; Kim, Euitae ; Kim, Jaeyoung ; Kittel-Schneider, Sarah ; Knowles, James A. ; Kogevinas, Manolis ; Kranz, Thorsten M. ; Krebs, Kristi ; Kushner, Steven A. ; Lavebratt, Catharina ; Lawrence, Jacob ; Leber, Markus ; Lee, Heon-Jeong ; Liao, Calwing ; Lucae, Susanne ; Lundberg, Martin ; MacIntyre, Donald J. ; Maier, Wolfgang ; Maihofer, Adam X. ; Malaspina, Dolores ; Manchia, Mirko ; Maratou, Eirini ; Martinsson, Lina ; Mattheisen, Manuel ; McGregor, Nathaniel W. ; McInnis, Melvin G. ; McKay, James D. ; Medeiros, Helena ; Meyer-Lindenberg, Andreas ; Millischer, Vincent ; Morris, Derek W. ; Moutsatsou, Paraskevi ; Mühleisen, Thomas W. ; O’Donovan, Claire ; Olsen, Catherine M. ; Panagiotaropoulou, Georgia ; Papiol, Sergi ; Pardiñas, Antonio F. ; Park, Hye Youn ; Perry, Amy ; Pfennig, Andrea ; Pisanu, Claudia ; Potash, James B. ; Quested, Digby ; Rapaport, Mark H. ; Regeer, Eline J. ; Rice, John P. ; Rivera, Margarita ; Schulte, Eva Christina ; Senner, Fanny ; Shadrin, Alexey ; Shilling, Paul D. ; Sigurdsson, Engilbert ; Sindermann, Lisa ; Sirignano, Lea ; Siskind, Dan ; Slaney, Claire ; Sloofman, Laura G. ; Smeland, Olav B. ; Smith, Daniel J. ; Sobell, Janet L. ; Soler Artigas, Maria ; Stein, Dan J. ; Stein, Frederike ; Su, Mei-Hsin ; Sung, Heejong ; Świątkowska, Beata ; Terao, Chikashi ; Tesfaye, Markos ; Tesli, Martin ; Thorgeirsson, Thorgeir E. ; Thorp, Jackson G. ; Toma, Claudio ; Tondo, Leonardo ; Tooney, Paul A. ; Tsai, Shih-Jen ; Tsermpini, Evangelia Eirini ; Vawter, Marquis P. ; Vedder, Helmut ; Vreeker, Annabel ; Walters, James T. R. ; Winsvold, Bendik S. ; Witt, Stephanie H. ; Won, Hong-Hee ; Ye, Robert ; Young, Allan H. ; Zandi, Peter P. ; Zillich, Lea ; Adolfsson, Rolf ; Alda, Martin ; Alfredsson, Lars ; Backlund, Lena ; Baune, Bernhard T. ; Bellivier, Frank ; Bengesser, Susanne ; Berrettini, Wade H. ; Biernacka, Joanna M. ; Boehnke, Michael ; Børglum, Anders D. ; Breen, Gerome ; Carr, Vaughan J. ; Catts, Stanley ; Cichon, Sven ; Corvin, Aiden ; Craddock, Nicholas ; Dannlowski, Udo ; Dikeos, Dimitris ; Etain, Bruno ; Ferentinos, Panagiotis ; Frye, Mark ; Fullerton, Janice M. ; Gawlik, Micha ; Gershon, Elliot S. ; Goes, Fernando S. ; Green, Melissa J. ; Grigoroiu-Serbanescu, Maria ; Hauser, Joanna ; Henskens, Frans A. ; Hjerling-Leffler, Jens ; Hougaard, David M. ; Hveem, Kristian ; Iwata, Nakao ; Jones, Ian ; Jones, Lisa A. ; Kahn, René S. ; Kelsoe, John R. ; Kircher, Tilo ; Kirov, George ; Kuo, Po-Hsiu ; Landén, Mikael ; Leboyer, Marion ; Li, Qingqin S. ; Lissowska, Jolanta ; Lochner, Christine ; Loughland, Carmel ; Luykx, Jurjen J. ; Martin, Nicholas G. ; Mathews, Carol A. ; Mayoral, Fermin ; McElroy, Susan L. ; McIntosh, Andrew M. ; McMahon, Francis J. ; Medland, Sarah E. ; Melle, Ingrid ; Milani, Lili ; Mitchell, Philip B. ; Morken, Gunnar ; Mors, Ole ; Mortensen, Preben Bo ; Müller-Myhsok, Bertram ; Myers, Richard M. ; Myung, Woojae ; Neale, Benjamin M. ; Nievergelt, Caroline M. ; Nordentoft, Merete ; Nöthen, Markus M. ; Nurnberger, John I. ; O’Donovan, Michael C. ; Oedegaard, Ketil J. ; Olsson, Tomas ; Owen, Michael J. ; Paciga, Sara A. ; Pantelis, Christos ; Pato, Carlos N. ; Pato, Michele T. ; Patrinos, George P. ; Pawlak, Joanna M. ; Ramos-Quiroga, Josep Antoni ; Reif, Andreas ; Reininghaus, Eva Z. ; Ribasés, Marta ; Rietschel, Marcella ; Ripke, Stephan ; Rouleau, Guy A. ; Roussos, Panos ; Saito, Takeo ; Schall, Ulrich ; Schalling, Martin ; Schofield, Peter R. ; Schulze, Thomas G. ; Scott, Laura J. ; Scott, Rodney J. ; Serretti, Alessandro ; Smoller, Jordan W. ; Squassina, Alessio ; Stahl, Eli A. ; Stefansson, Hreinn ; Stefansson, Kari ; Stordal, Eystein ; Streit, Fabian ; Sullivan, Patrick F. ; Turecki, Gustavo ; Vaaler, Arne E. ; Vieta, Eduard ; Vincent, John B. ; Waldman, Irwin D. ; Weickert, Cynthia S. ; Weickert, Thomas W. ; Werge, Thomas ; Whiteman, David C. ; Zwart, John-Anker ; Edenberg, Howard J. ; McQuillin, Andrew ; Forstner, Andreas J. ; Mullins, Niamh ; Di Florio, Arianna ; Ophoff, Roel A. ; Andreassen, Ole A.
Pati, Sarthak ; Baid, Ujjwal ; Edwards, Brandon ; Sheller, Micah ; Wang, Shih-Han ; Reina, G. Anthony ; Foley, Patrick ; Gruzdev, Alexey ; Karkada, Deepthi ; Davatzikos, Christos ; Sako, Chiharu ; Ghodasara, Satyam ; Bilello, Michel ; Mohan, Suyash ; Vollmuth, Philipp ; Brugnara, Gianluca ; Jayachandran Preetha, Chandrakanth ; Sahm, Felix ; Maier-Hein, Klaus ; Zenk, Maximilian ; Bendszus, Martin ; Wick, Wolfgang ; Calabrese, Evan ; Rudie, Jeffrey ; Villanueva-Meyer, Javier ; Cha, Soonmee ; Ingalhalikar, Madhura ; Jadhav, Manali ; Pandey, Umang ; Saini, Jitender ; Garrett, John ; Larson, Matthew ; Jeraj, Robert ; Currie, Stuart ; Frood, Russell ; Fatania, Kavi ; Huang, Raymond Y. ; Chang, Ken ; Balaña, Carmen ; Capellades, Jaume ; Puig, Josep ; Trenkler, Johannes ; Pichler, Josef ; Necker, Georg ; Haunschmidt, Andreas ; Meckel, Stephan ; Shukla, Gaurav ; Liem, Spencer ; Alexander, Gregory S. ; Lombardo, Joseph ; Palmer, Joshua D. ; Flanders, Adam E. ; Dicker, Adam P. ; Sair, Haris I. ; Jones, Craig K. ; Venkataraman, Archana ; Jiang, Meirui ; So, Tiffany Y. ; Chen, Cheng ; Heng, Pheng Ann ; Dou, Qi ; Kozubek, Michal ; Lux, Filip ; Michálek, Jan ; Matula, Petr ; Keřkovský, Miloš ; Kopřivová, Tereza ; Dostál, Marek ; Vybíhal, Václav ; Vogelbaum, Michael A. ; Mitchell, J. Ross ; Farinhas, Joaquim ; Maldjian, Joseph A. ; Bangalore Yogananda, Chandan Ganesh ; Pinho, Marco C. ; Reddy, Divya ; Holcomb, James ; Wagner, Benjamin C. ; Ellingson, Benjamin M. ; Cloughesy, Timothy F. ; Raymond, Catalina ; Oughourlian, Talia ; Hagiwara, Akifumi ; Wang, Chencai ; To, Minh-Son ; Bhardwaj, Sargam ; Chong, Chee ; Agzarian, Marc ; Falcão, Alexandre Xavier ; Martins, Samuel B. ; Teixeira, Bernardo Corrêa de Almeida ; Sprenger, Flávia ; Menotti, David ; Lucio, Diego R. ; LaMontagne, Pamela ; Marcus, Daniel ; Wiestler, Benedikt ; Kofler, Florian ; Ezhov, Ivan ; Metz, Marie ; Jain, Rajan ; Lee, Matthew ; Lui, Yvonne W. ; McKinley, Richard ; Slotboom, Johannes ; Radojewski, Piotr ; Meier, Raphael ; Wiest, Roland Gerhard Rudi ; Murcia, Derrick ; Fu, Eric ; Haas, Rourke ; Thompson, John ; Ormond, David Ryan ; Badve, Chaitra ; Sloan, Andrew E. ; Vadmal, Vachan ; Waite, Kristin ; Colen, Rivka R. ; Pei, Linmin ; Ak, Murat ; Srinivasan, Ashok ; Bapuraj, Jayapalli Rajiv ; Rao, Arvind ; Wang, Nicholas ; Yoshiaki, Ota ; Moritani, Toshio ; Turk, Sevcan ; Lee, Joonsang ; Prabhudesai, Snehal ; Morón, Fanny ; Mandel, Jacob ; Kamnitsas, Konstantinos ; Glocker, Ben ; Dixon, Luke V. M. ; Williams, Matthew ; Zampakis, Peter ; Panagiotopoulos, Vasileios ; Tsiganos, Panagiotis ; Alexiou, Sotiris ; Haliassos, Ilias ; Zacharaki, Evangelia I. ; Moustakas, Konstantinos ; Kalogeropoulou, Christina ; Kardamakis, Dimitrios M. ; Choi, Yoon Seong ; Lee, Seung-Koo ; Chang, Jong Hee ; Ahn, Sung Soo ; Luo, Bing ; Poisson, Laila ; Wen, Ning ; Tiwari, Pallavi ; Verma, Ruchika ; Bareja, Rohan ; Yadav, Ipsa ; Chen, Jonathan ; Kumar, Neeraj ; Smits, Marion ; Voort, Sebastian R. van der ; Alafandi, Ahmed ; Incekara, Fatih ; Wijnenga, Maarten M. J. ; Kapsas, Georgios ; Gahrmann, Renske ; Schouten, Joost W. ; Dubbink, Hendrikus J. ; Vincent, Arnaud J. P. E. ; Van den Bent, Martin J. ; French, Pim J. ; Klein, Stefan ; Yuan, Yading ; Sharma, Sonam ; Tseng, Tzu-Chi ; Adabi, Saba ; Niclou, Simone P. ; Keunen, Olivier ; Hau, Ann-Christin ; Vallières, Martin ; Fortin, David ; Lepage, Martin ; Landman, Bennett ; Ramadass, Karthik ; Xu, Kaiwen ; Chotai, Silky ; Chambless, Lola B. ; Mistry, Akshitkumar ; Thompson, Reid C. ; Gusev, Yuriy ; Bhuvaneshwar, Krithika ; Sayah, Anousheh ; Bencheqroun, Camelia ; Belouali, Anas ; Madhavan, Subha ; Booth, Thomas C. ; Chelliah, Alysha ; Modat, Marc ; Shuaib, Haris ; Dragos, Carmen ; Abayazeed, Aly ; Kolodziej, Kenneth ; Hill, Michael ; Abbassy, Ahmed ; Gamal, Shady ; Mekhaimar, Mahmoud ; Qayati, Mohamed ; Reyes, Mauricio ; Park, Ji Eun ; Yun, Jihye ; Kim, Ho Sung ; Mahajan, Abhishek ; Muzi, Mark ; Benson, Sean ; Beets-Tan, Regina G. H. ; Teuwen, Jonas ; Herrera-Trujillo, Alejandro ; Trujillo, Maria ; Escobar, William ; Abello, Ana Lorena ; Bernal, Jose ; Gómez, Jhon ; Choi, Joseph ; Baek, Stephen ; Kim, Yusung ; Ismael, Heba ; Allen, Bryan ; Buatti, John M. ; Kotrotsou, Aikaterini ; Li, Hongwei ; Weiss, Tobias ; Weller, Michael ; Bink, Andrea ; Pouymayou, Bertrand ; Shaykh, Hassan F. ; Saltz, Joel ; Prasanna, Prateek ; Shrestha, Sampurna ; Mani, Kartik M. ; Payne, David ; Kurc, Tahsin ; Pelaez, Enrique ; Franco-Maldonado, Heydy ; Loayza, Francis ; Quevedo Sacoto, Andrés Sebastián ; Guevara, Pamela ; Torche, Esteban ; Mendoza, Cristobal ; Vera, Franco ; Ríos, Elvis ; López, Eduardo ; Velastin, Sergio Alejandro ; Ogbole, Godwin ; Soneye, Mayowa ; Oyekunle, Dotun ; Odafe-Oyibotha, Olubunmi ; Osobu, Babatunde ; Shu’aibu, Mustapha ; Dorcas, Adeleye ; Dako, Farouk ; Simpson, Amber L. ; Hamghalam, Mohammad ; Peoples, Jacob J. ; Hu, Ricky ; Tran, Anh ; Cutler, Danielle ; Moraes, Fabio Y. ; Boss, Michael A. ; Gimpel, James ; Kattil Veettil, Deepak ; Schmidt, Kendall ; Bialecki, Brian ; Marella, Sailaja ; Price, Cynthia ; Cimino, Lisa ; Apgar, Charles ; Shah, Prashant ; Menze, Bjoern Holger ; Barnholtz-Sloan, Jill S. ; Martin, Jason ; Bakas, Spyridon
Pati, Sarthak ; Baid, Ujjwal ; Edwards, Brandon ; Sheller, Micah ; Wang, Shih-Han ; Reina, G. Anthony ; Foley, Patrick ; Gruzdev, Alexey ; Karkada, Deepthi ; Davatzikos, Christos ; Sako, Chiharu ; Ghodasara, Satyam ; Bilello, Michel ; Mohan, Suyash ; Vollmuth, Philipp ; Brugnara, Gianluca ; Jayachandran Preetha, Chandrakanth ; Sahm, Felix ; Maier-Hein, Klaus ; Zenk, Maximilian ; Bendszus, Martin ; Wick, Wolfgang ; Calabrese, Evan ; Rudie, Jeffrey ; Villanueva-Meyer, Javier ; Cha, Soonmee ; Ingalhalikar, Madhura ; Jadhav, Manali ; Pandey, Umang ; Saini, Jitender ; Garrett, John ; Larson, Matthew ; Jeraj, Robert ; Currie, Stuart ; Frood, Russell ; Fatania, Kavi ; Huang, Raymond Y. ; Chang, Ken ; Balaña, Carmen ; Capellades, Jaume ; Puig, Josep ; Trenkler, Johannes ; Pichler, Josef ; Necker, Georg ; Haunschmidt, Andreas ; Meckel, Stephan ; Shukla, Gaurav ; Liem, Spencer ; Alexander, Gregory S. ; Lombardo, Joseph ; Palmer, Joshua D. ; Flanders, Adam E. ; Dicker, Adam P. ; Sair, Haris I. ; Jones, Craig K. ; Venkataraman, Archana ; Jiang, Meirui ; So, Tiffany Y. ; Chen, Cheng ; Heng, Pheng Ann ; Dou, Qi ; Kozubek, Michal ; Lux, Filip ; Michálek, Jan ; Matula, Petr ; Keřkovský, Miloš ; Kopřivová, Tereza ; Dostál, Marek ; Vybíhal, Václav ; Vogelbaum, Michael A. ; Mitchell, J. Ross ; Farinhas, Joaquim ; Maldjian, Joseph A. ; Bangalore Yogananda, Chandan Ganesh ; Pinho, Marco C. ; Reddy, Divya ; Holcomb, James ; Wagner, Benjamin C. ; Ellingson, Benjamin M. ; Cloughesy, Timothy F. ; Raymond, Catalina ; Oughourlian, Talia ; Hagiwara, Akifumi ; Wang, Chencai ; To, Minh-Son ; Bhardwaj, Sargam ; Chong, Chee ; Agzarian, Marc ; Falcão, Alexandre Xavier ; Martins, Samuel B. ; Teixeira, Bernardo Corrêa de Almeida ; Sprenger, Flávia ; Menotti, David ; Lucio, Diego R. ; LaMontagne, Pamela ; Marcus, Daniel ; Wiestler, Benedikt ; Kofler, Florian ; Ezhov, Ivan ; Metz, Marie ; Jain, Rajan ; Lee, Matthew ; Lui, Yvonne W. ; McKinley, Richard ; Slotboom, Johannes ; Radojewski, Piotr ; Meier, Raphael ; Wiest, Roland Gerhard Rudi ; Murcia, Derrick ; Fu, Eric ; Haas, Rourke ; Thompson, John ; Ormond, David Ryan ; Badve, Chaitra ; Sloan, Andrew E. ; Vadmal, Vachan ; Waite, Kristin ; Colen, Rivka R. ; Pei, Linmin ; Ak, Murat ; Srinivasan, Ashok ; Bapuraj, Jayapalli Rajiv ; Rao, Arvind ; Wang, Nicholas ; Yoshiaki, Ota ; Moritani, Toshio ; Turk, Sevcan ; Lee, Joonsang ; Prabhudesai, Snehal ; Morón, Fanny ; Mandel, Jacob ; Kamnitsas, Konstantinos ; Glocker, Ben ; Dixon, Luke V. M. ; Williams, Matthew ; Zampakis, Peter ; Panagiotopoulos, Vasileios ; Tsiganos, Panagiotis ; Alexiou, Sotiris ; Haliassos, Ilias ; Zacharaki, Evangelia I. ; Moustakas, Konstantinos ; Kalogeropoulou, Christina ; Kardamakis, Dimitrios M. ; Choi, Yoon Seong ; Lee, Seung-Koo ; Chang, Jong Hee ; Ahn, Sung Soo ; Luo, Bing ; Poisson, Laila ; Wen, Ning ; Tiwari, Pallavi ; Verma, Ruchika ; Bareja, Rohan ; Yadav, Ipsa ; Chen, Jonathan ; Kumar, Neeraj ; Smits, Marion ; Voort, Sebastian R. van der ; Alafandi, Ahmed ; Incekara, Fatih ; Wijnenga, Maarten M. J. ; Kapsas, Georgios ; Gahrmann, Renske ; Schouten, Joost W. ; Dubbink, Hendrikus J. ; Vincent, Arnaud J. P. E. ; Van den Bent, Martin J. ; French, Pim J. ; Klein, Stefan ; Yuan, Yading ; Sharma, Sonam ; Tseng, Tzu-Chi ; Adabi, Saba ; Niclou, Simone P. ; Keunen, Olivier ; Hau, Ann-Christin ; Vallières, Martin ; Fortin, David ; Lepage, Martin ; Landman, Bennett ; Ramadass, Karthik ; Xu, Kaiwen ; Chotai, Silky ; Chambless, Lola B. ; Mistry, Akshitkumar ; Thompson, Reid C. ; Gusev, Yuriy ; Bhuvaneshwar, Krithika ; Sayah, Anousheh ; Bencheqroun, Camelia ; Belouali, Anas ; Madhavan, Subha ; Booth, Thomas C. ; Chelliah, Alysha ; Modat, Marc ; Shuaib, Haris ; Dragos, Carmen ; Abayazeed, Aly ; Kolodziej, Kenneth ; Hill, Michael ; Abbassy, Ahmed ; Gamal, Shady ; Mekhaimar, Mahmoud ; Qayati, Mohamed ; Reyes, Mauricio ; Park, Ji Eun ; Yun, Jihye ; Kim, Ho Sung ; Mahajan, Abhishek ; Muzi, Mark ; Benson, Sean ; Beets-Tan, Regina G. H. ; Teuwen, Jonas ; Herrera-Trujillo, Alejandro ; Trujillo, Maria ; Escobar, William ; Abello, Ana Lorena ; Bernal, Jose ; Gómez, Jhon ; Choi, Joseph ; Baek, Stephen ; Kim, Yusung ; Ismael, Heba ; Allen, Bryan ; Buatti, John M. ; Kotrotsou, Aikaterini ; Li, Hongwei ; Weiss, Tobias ; Weller, Michael ; Bink, Andrea ; Pouymayou, Bertrand ; Shaykh, Hassan F. ; Saltz, Joel ; Prasanna, Prateek ; Shrestha, Sampurna ; Mani, Kartik M. ; Payne, David ; Kurc, Tahsin ; Pelaez, Enrique ; Franco-Maldonado, Heydy ; Loayza, Francis ; Quevedo Sacoto, Andrés Sebastián ; Guevara, Pamela ; Torche, Esteban ; Mendoza, Cristobal ; Vera, Franco ; Ríos, Elvis ; López, Eduardo ; Velastin, Sergio Alejandro ; Ogbole, Godwin ; Soneye, Mayowa ; Oyekunle, Dotun ; Odafe-Oyibotha, Olubunmi ; Osobu, Babatunde ; Shu’aibu, Mustapha ; Dorcas, Adeleye ; Dako, Farouk ; Simpson, Amber L. ; Hamghalam, Mohammad ; Peoples, Jacob J. ; Hu, Ricky ; Tran, Anh ; Cutler, Danielle ; Moraes, Fabio Y. ; Boss, Michael A. ; Gimpel, James ; Kattil Veettil, Deepak ; Schmidt, Kendall ; Bialecki, Brian ; Marella, Sailaja ; Price, Cynthia ; Cimino, Lisa ; Apgar, Charles ; Shah, Prashant ; Menze, Bjoern Holger ; Barnholtz-Sloan, Jill S. ; Martin, Jason ; Bakas, Spyridon
Meyer, Claus ; Hofmann, J ; Burmeister, Thomas ; Gröger, D ; Park, TS ; Emerenciano, M ; Pombo de Oliveira, M ; Renneville, A ; Macintyre, E ; Cavé, H ; Clappier, E ; Mass-Malo, K ; Zuna, J ; Trka, J ; De Braekeleer, E ; De Braekeleer, M ; Oh, SH ; Tsaur, G ; Fechina, L ; van der Velden, VH ; van Dongen, JJ ; Delabesse, E ; Binato, R ; Silva, ML ; Kustanovich, A ; Aleinikova, O ; Harris, MH ; Lund-Aho, T ; Juvonen, V ; Heidenreich, Olaf Torben ; Vormoor, J ; Choi, WW ; Jarosova, M ; Kolenova, A ; Bueno, C ; Menendez, P ; Wehner, S ; Eckert, Cornelia ; Talmant, P ; Tondeur, S ; Lippert, E ; Launay, E ; Henry, C ; Ballerini, P ; Lapillone, H ; Callanan, MB ; Cayuela, JM ; Herbaux, C ; Cazzaniga, G ; Kakadiya, PM ; Bohlander, Stefan Klaus ; Ahlmann, M ; Choi, JR ; Gameiro, P ; Lee, DS ; Krauter, J ; Cornillet-Lefebvre, P ; Te Kronnie, G ; Schäfer, BW ; Kubetzko, S ; Alonso, CN ; zur Stadt, U ; Sutton, R ; Venn, NC ; Izraeli, S ; Trakhtenbrot, L ; Madsen, HO ; Archer, P ; Hancock, J ; Cerveira, N ; Teixeira, MR ; Lo Nigro, L ; Möricke, A ; Stanulla, M ; Schrappe, M ; Sedék, L ; Szczepański, T ; Zwaan, CM ; Coenen, EA ; van den Heuvel-Eibrink, MM ; Strehl, S ; Dworzak, Michael N. ; Panzer-Grümayer, Renate ; Dingermann, Theodor ; Klingebiel, Thomas ; Marschalek, Rolf
Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (~ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.
Jarick, Ivonne ; Volckmar, Anna-Lena ; Pütter, Carolin ; Pechlivanis, Sonali ; Nguyen, Trang T. ; Dauvermann, Maria R. ; Beck, Sebastian ; Albayrak, Özgür ; Scherag, Susann ; Gilsbach, Susanne ; Cichon, Sven ; Hoffmann, Per ; Degenhardt, Franziska ; Nöthen, Markus Maria ; Schreiber, Stefan ; Wichmann, Heinz Erich ; Jöckel, Karl-Heinz ; Heinrich, Joachim ; Tiesler, Carla Marie Thérèse ; Faraone, Stephen V. ; Walitza, Susanne ; Sinzig, Judith ; Freitag, Christine M. ; Meyer, Jobst ; Herpertz-Dahlmann, Beate ; Lehmkuh, Gerd ; Renner, Tobias J. ; Warnke, Andreas ; Romanos, Marcel ; Lesch, Klaus-Peter J. ; Reif, Andreas ; Schimmelmann, Benno G. ; Hebebrand, Johannes ; Scherag, André ; Hinney, Anke
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
Westfall, Gary D. ; Gosset, Jean ; Johansen, P. J. ; Poskanzer, Arthur M. ; Meyer, W.G ; Gutbrod, Hans Herbert ; Sandoval, Andres ; Stock, Reinhard
A simple model is proposed for the emission of nucleons with velocities intermediate between those of the target and projectile. In this model, the nucleons which are mutually swept out from the target and projectile form a hot quasiequilibrated fireball which decays as an ideal gas. The overall features of the proton-inclusive spectra from 250- and 400-MeV/nucleon 20Ne ions and 400-MeV/nucleon 4He ions interacting with uranium are fitted without any adjustable parameters.
Wolff, Anette Susanne Bøe ; Mitchell, Anna L. ; Cordell, Heather J. ; Short, Andrea ; Skinningsrud, Beate ; Ollier, William ; Badenhoop, Klaus ; Meyer, Gesine ; Falorni, Alberto ; Kämpe, Olle ; Undlien, Dag ; Pearce, Simon H. S. ; Husebye, Eystein S.
In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.
Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts
(2014)
Mitchell, Anna L. ; Macarthur, Katie D. R. ; Gan, Earn H. ; Baggott, Lucy E. ; Wolff, Anette S. B. ; Skinningsrud, Beate ; Platt, Hazel ; Short, Andrea ; Lobell, Anna ; Kämpe, Olle ; Bensing, Sophie ; Betterle, Corrado ; Kasperlik-Zaluska, Anna ; Zurawek, Magdalena ; Fichna, Marta ; Kockum, Ingrid ; Nordling Eriksson, Gabriel ; Ekwall, Olov ; Wahlberg, Jeanette ; Dahlqvist, Per ; Hulting, Anna-Lena ; Penna Martinez, Marissa ; Meyer, Gesine ; Kahles, Heinrich ; Badenhoop, Klaus ; Hahner, Stephanie ; Quinkler, Marcus ; Falorni, Alberto ; Phipps-Green, Amanda ; Merriman, Tony R. ; Ollier, William ; Cordell, Heather J. ; Undlien, Dag ; Czarnocka, Barbara ; Husebye, Eystein ; Pearce, Simon H. S.
Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.
Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.
Methods: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity.
Results: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively.
Conclusions: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
Höfer, Hubert ; Astrin, Jonas J. ; Holstein, Joachim ; Spelda, Jörg ; Meyer, Franziska ; Zarte, Natalie
The usefulness of propylene glycol as capture preservative in pitfall traps, with the aim of using the captured spiders for DNA barcoding, was tested. For this purpose a laboratory experiment on the conserving and/or denaturing effect of propylene glycol on mitochondrial DNA (COI) was set up. For the experiment 110 specimens of the common and abundant wolf spider species Pardosa lugubris were manually captured, killed and incubated from one to four weeks in either pure or watered propylene glycol or 70 % denatured ethanol. Rates of successful sequencing, following a standard protocol, did not differ between samples incubated in propylene glycol and in the more commonly used ethanol. Thus, within four weeks, propylene glycol did not significantly denaturize mitochondrial DNA. In two field studies, pitfall traps with propylene glycol captured more spiders than traps with acetic acid. The effect was significant only in one of two field trials, but then consistent at three different sites and the three dominant spider families. Based on these results and our operating experience, we recommend propylene glycol as a capture preservative for (pitfall) traps to obtain specimens for DNA barcoding identification.
Dell'Ampio, Emiliano ; Meusemann, Karen ; Szucsich, Nikolaus Urban ; Peters, Ralph S. ; Meyer, Benjamin ; Borner, Janus ; Petersen, Malte ; Aberer, Andre J. ; Stamatakis, Alexandros ; Walz, Manfred G. ; Minh, Bui Quang ; Haeseler, Arndt von ; Ebersberger, Ingo ; Pass, Günther ; Misof, Bernhard
Phylogenetic relationships of the primarily wingless insects are still considered unresolved. Even the most comprehensive phylogenomic studies that addressed this question did not yield congruent results. In order to get a grip on these problems, we here analyzed the sources of incongruence in these phylogenomic studies using an extended transcriptome dataset.Our analyses showed that unevenly distributed missing data can be severely misleading by inflating node support despite the absence of phylogenetic signal. In consequence, only decisive datasets should be used which exclusively comprise data blocks containing all taxa whose relationships are addressed. Additionally, we employed Four-cluster Likelihood-Mapping (FcLM) to measure the degree of congruence among genes of a dataset, as a measure of support alternative to bootstrap. FcLM showed incongruent signal among genes, which in our case is correlated with neither functional class assignment of these genes, nor with model misspecification due to unpartitioned analyses. The herein analyzed dataset is the currently largest dataset covering primarily wingless insects, but failed to elucidate their interordinal phylogenetic relationships. While this is unsatisfying from a phylogenetic perspective, we try to show that the analyses of structure and signal within phylogenomic data can protect us from biased phylogenetic inferences due to analytical artefacts.
Hereditary angioedema (HAE) in children and adolescents : a consensus on therapeutic strategies
(2012)
Wahn, Volker ; Aberer, Werner ; Eberl, Wolfgang ; Faßhauer, Maria ; Kühne, Thomas ; Kurnik, Karin ; Magerl, Markus ; Meyer-Olson, Dirk ; Martinez Saguer, Inmaculada ; Späth, Peter J. ; Staubach-Renz, Petra ; Kreuz, Wolfhart
Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.
(NBu4)2[Co4(SPh)6Cl4] (1) and [Co4(SPh)6CU(PPh3)2] (2) are prepared by the reaction of (NBu4)[CoCl3(PPh3)] and [CoCl2(PPh3)2] with PhSSiMe3 in toluene solution. The overall description of the Co4S6Cl4 core is that o f a nearly regular Co4-tetrahedron inscribed in an irregular octahedron of the bridging S atoms resulting in an “adamantane” type cage. 1 reacts with Na[Mn(CO)5] to form the dinuclear complex (NBu4)[Mn2(SPh)3(CO)6] (4). Each Mn atom is bound to three CO and three μ2-SPh ligands. The Mn-Mn contact (318.5 pm) does not indicate metal-metal bonding.
Kieffer, Tara L. ; De Meyer, Sandra ; Bartels, Doug J. ; Sullivan, James C. ; Zhang, Eileen Z. ; Tigges, Ann ; Dierynck, Inge ; Spanks, Joan ; Dorrian, Jennifer ; Jiang, Min ; Adiwijaya, Bambang ; Ghys, Anne ; Beumont, Maria ; Kauffman, Robert S. ; Adda, Nathalie ; Jacobson, Ira M. ; Sherman, Kenneth E. ; Zeuzem, Stefan ; Kwong, Ann D. ; Picchio, Gaston
Background: In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR.
Methods: Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment.
Results: Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients.
Conclusions: A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment.
Blankenbach, Kira Vanessa ; Claas, Ralf Frederik ; Aster, Natalie Judith ; Spohner, Anna Katharina ; Trautmann, Sandra ; Ferreirós Bouzas, Nerea ; Black, Justin L. ; Tesmer, John J. G. ; Offermanns, Stefan ; Wieland, Thomas ; Meyer zu Heringdorf, Dagmar
Diverse extracellular signals induce plasma membrane translocation of sphingosine kinase-1 (SphK1), thereby enabling inside-out signaling of sphingosine-1-phosphate. We have shown before that Gq-coupled receptors and constitutively active Gαq/11 specifically induced a rapid and long-lasting SphK1 translocation, independently of canonical Gq/phospholipase C (PLC) signaling. Here, we further characterized Gq/11 regulation of SphK1. SphK1 translocation by the M3 receptor in HEK-293 cells was delayed by expression of catalytically inactive G-protein-coupled receptor kinase-2, p63Rho guanine nucleotide exchange factor (p63RhoGEF), and catalytically inactive PLCβ3, but accelerated by wild-type PLCβ3 and the PLCδ PH domain. Both wild-type SphK1 and catalytically inactive SphK1-G82D reduced M3 receptor-stimulated inositol phosphate production, suggesting competition at Gαq. Embryonic fibroblasts from Gαq/11 double-deficient mice were used to show that amino acids W263 and T257 of Gαq, which interact directly with PLCβ3 and p63RhoGEF, were important for bradykinin B2 receptor-induced SphK1 translocation. Finally, an AIXXPL motif was identified in vertebrate SphK1 (positions 100–105 in human SphK1a), which resembles the Gαq binding motif, ALXXPI, in PLCβ and p63RhoGEF. After M3 receptor stimulation, SphK1-A100E-I101E and SphK1-P104A-L105A translocated in only 25% and 56% of cells, respectively, and translocation efficiency was significantly reduced. The data suggest that both the AIXXPL motif and currently unknown consequences of PLCβ/PLCδ(PH) expression are important for regulation of SphK1 by Gq/11.
Gutbrod, Hans Herbert ; Sandoval, Andres ; Johansen, P. J. ; Poskanzer, Arthur M. ; Gosset, Jean ; Meyer, W. G. ; Westfall, Gary D. ; Stock, Reinhard
Double-differential cross sections have been measured for high-energy p, d, t, 3He, and 4He particles emitted from uranium targets irradiated with 20Ne ions at energies of 250, 400, and 2100 MeV/nucleon and 4He ions at 400 MeV/nucleon. By using the shape and yield of the proton energy spectra, the shape and yield of the d, t, 3He, and 4He energy spectra can be deduced at all measured angles for all incident projectile energies by assuming that they are formed by a coalescence of cascade nucleons, using a model analogous to that of Butler and Pearson, and Schwarzschild and Zupancic-caron.
Lopes, Bruno Almeida ; Meyer, Claus ; Conceição Barbosa, Thayana ; Poubel, Caroline P. ; Mansur, Marcela Braga ; Duployez, Nicolas ; Bashton, Matthew ; Harrison, Christine J. ; Zur Stadt, Udo ; Horstmann, Martin ; Pombo-de-Oliveira, Maria S. ; Palmi, Chiara ; Cazzaniga, Gianni ; Venn, Nicola C. ; Sutton, Rosemary ; Alonso, Cristina N. ; Tsaur, Grigory ; Gupta, Sanjeev ; Bakhshi, Sameer ; Marschalek, Rolf ; Emerenciano, Mariana
IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in both childhood and adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Previously, we revealed that COBL is a hotspot for breakpoints in leukemia and could promote IKZF1 deletions. Through an international collaboration, we provide a detailed genetic and clinical picture of B-ALL with COBL rearrangements (COBL-r). Patients with B-ALL and IKZF1 deletion (n = 133) were included. IKZF1 ∆1-8 were associated with large alterations within chromosome 7: monosomy 7 (18%), isochromosome 7q (10%), 7p loss (19%), and interstitial deletions (53%). The latter included COBL-r, which were found in 12% of the IKZF1 ∆1-8 cohort. Patients with COBL-r are mostly classified as intermediate cytogenetic risk and frequently harbor ETV6, PAX5, CDKN2A/B deletions. Overall, 56% of breakpoints were located within COBL intron 5. Cryptic recombination signal sequence motifs were broadly distributed within the sequence of COBL, and no enrichment for the breakpoint cluster region was found. In summary, a diverse spectrum of alterations characterizes ΔIKZF1 and they also include deletion breakpoints within COBL. We confirmed that COBL is a hotspot associated with ΔIKZF1, but these rearrangements are not driven by RAG-mediated recombination.
Chang, Johannes ; Höfer, Pauline ; Böhling, Nina ; Lingohr, Philipp ; Manekeller, Steffen ; Kalff, Jörg C. ; Dohmen, Jonas ; Kaczmarek, Dominik J. ; Jansen, Christian ; Meyer, Carsten ; Straßburg, Christian P. ; Trebicka, Jonel ; Praktiknjo, Michael
Background & Aims: Acute-on-chronic liver failure (ACLF) is a syndrome associated with organ failure and high short-term mortality. Recently, the role of surgery as a precipitating event for ACLF has been characterised. However, the impact of preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement on ACLF development in patients with cirrhosis undergoing surgery has not been investigated yet.
Methods: A total of 926 patients (363 with cirrhosis undergoing surgery and 563 patients with TIPS) were screened. Forty-five patients with preoperative TIPS (TIPS group) were 1:1 propensity matched to patients without preoperative TIPS (no-TIPS group). The primary endpoint was the development of ACLF within 28 and 90 days after surgery. The secondary endpoint was 1-year mortality. Results were confirmed by a differently 1:2 matched cohort (n = 176).
Results: Patients in the no-TIPS group had significantly higher rates of ACLF within 28 days (29 vs. 9%; p = 0.016) and 90 days (33 vs. 13%; p = 0.020) after surgery as well as significantly higher 1-year mortality (38 vs. 18%; p = 0.023) compared with those in the TIPS group. Surgery without preoperative TIPS and Chronic Liver Failure Consortium–Acute Decompensation (CLIF-C AD) score were independent predictors for 28- and 90-day ACLF development and 1-year mortality after surgery, especially in patients undergoing visceral surgery. In the no-TIPS group, a CLIF-C AD score of >45 could be identified as cut-off for patients at risk for postoperative ACLF development benefiting from TIPS.
Conclusions: This study suggests that preoperative TIPS may result in lower rates of postoperative ACLF development especially in patients undergoing visceral surgery and with a CLIF-C AD score above 45.
Lay summary: Acute-on-chronic liver failure (ACLF) is a syndrome that is associated with high short-term mortality. Surgical procedures are a known precipitating event for ACLF. This study investigates the role of preoperative insertion of a transjugular intrahepatic portosystemic shunt (TIPS) on postoperative mortality and ACLF development. Patients with TIPS insertion before a surgical procedure exhibit improved postoperative survival and lower rates of postoperative ACLF, especially in patients undergoing visceral surgery and with a high CLIF-C AD prognostic score. Thus, this study suggests preoperative TIPS insertion in those high-risk patients.