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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. 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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. 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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.
Randall, Joshua C. ; Winkler, Thomas W. ; Kutalik, Zoltán ; I. Berndt, Sonja ; Jackson, Anne U. ; Monda, Keri L. ; Kilpeläinen, Tuomas O. ; Esko, Tõnu ; Mägi, Reedik ; Li, Shengxu ; Workalemahu, Tsegaselassie ; Feitosa, Mary F. ; Croteau-Chonka, Damien C. ; Day, Felix R. ; Fall, Tove ; Ferreira, Teresa ; Gustafsson, Stefan ; Locke, Adam E. ; Mathieson, Iain ; Scherag, André ; Vedantam, Sailaja ; Wood, Andrew R. ; Liang, Liming ; Steinthorsdottir, Valgerdur ; Thorleifsson, Gudmar ; Dermitzakis, Emmanouil T. ; Dimas, Antigone S. ; Karpe, Fredrik ; Min, Josine L. ; Nicholson, George ; Clegg, Deborah J. ; Person, Thomas ; Krohn, Jon P. ; Bauer, Sabrina ; Buechler, Christa ; Eisinger, Kristina ; Bonnefond, Amélie ; Froguel, Philippe ; Hottenga, Jouke-Jan ; Prokopenko, Inga ; Waite, Lindsay L. ; Harris, Tamara B. ; Smith, Albert Vernon ; Shuldiner, Alan R. ; McArdle, Wendy L. ; Caulfield, Mark J. ; Munroe, Patricia B. ; Grönberg, Henrik ; Chen, Yii-Der Ida ; Li, Guo ; Beckmann, Jacques S. ; Johnson, Toby ; Thorsteinsdottir, Unnur ; Teder-Laving, Maris ; Khaw, Kay-Tee ; Wareham, Nicholas J. ; Zhao, Jing Hua ; Amin, Najaf ; Oostra, Ben A. ; Kraja, Aldi T. ; Province, Michael A. ; Cupples, L. Adrienne ; Heard-Costa, Nancy L. ; Kaprio, Jaakko ; Ripatti, Samuli ; Surakka, Ida ; Collins, Francis S. ; Saramies, Jouko ; Tuomilehto, Jaakko ; Jula, Antti ; Salomaa, Veikko ; Erdmann, Jeanette ; Hengstenberg, Christian ; Loley, Christina ; Schunkert, Heribert ; Lamina, Claudia ; Wichmann, Heinz Erich ; Albrecht, Eva ; Gieger, Christian ; Hicks, Andrew A. ; Johansson, Åsa ; Pramstaller, Peter P. ; Kathiresan, Sekar ; Speliotes, Elizabeth K. ; Penninx, Brenda W. J. H. ; Hartikainen, Anna-Liisa ; Jarvelin, Marjo-Riitta ; Gyllensten, Ulf ; Boomsma, Dorret I. ; Campbell, Harry ; Wilson, James F. ; Chanock, Stephen J. ; Farrall, Martin ; Goel, Anuj ; Medina-Gomez, Carolina ; Rivadeneira, Fernando ; Estrada, Karol ; Uitterlinden, André G. ; Hofman, Albert ; Zillikens, M. Carola ; Heijer, Martin den ; Kiemeney, Lambertus Adrianus ; Maschio, Andrea ; Hall, Per ; Tyrer, Jonathan ; Teumer, Alexander ; Völzke, Henry ; Kovacs, Peter ; Tönjes, Anke ; Mangino, Massimo ; Spector, Tim D. ; Hayward, Caroline ; Rudan, Igor ; Hall, Alistair S. ; Samani, Nilesh J. ; Attwood, Antony Paul ; Sambrook, Jennifer G. ; Hung, Joseph ; Palmer, Lyle J. ; Lokki, Marja-Liisa ; Sinisalo, Juha ; Boucher, Gabrielle ; Huikuri, Heikki ; Lorentzon, Mattias ; Ohlsson, Claes ; Eklund, Niina ; Eriksson, Johan G. ; Barlassina, Cristina ; Rivolta, Carlo ; Nolte, Ilja M. ; Snieder, Harold ; Klauw, Melanie M. van der ; Vliet-Ostaptchouk, Jana V. van ; Gejman, Pablo V. ; Shi, Jianxin ; Jacobs, Kevin B. ; Wang, Zhaoming ; Bakker, Stephan J. L. ; Mateo Leach, Irene ; Navis, Gerjan ; Harst, Pim van der ; Martin, Nicholas Gordon ; Medland, Sarah E. ; Montgomery, Grant W. ; Yang, Jian ; Chasman, Daniel I. ; Ridker, Paul M. ; Rose, Lynda M. ; Lehtimäki, Terho ; Raitakari, Olli ; Absher, Devin ; Iribarren, Carlos ; Basart, Hanneke ; Hovingh, Kees G. ; Hyppönen, Elina ; Power, Chris ; Power, Chris ; Anderson, Denise ; Beilby, John P. ; Hui, Jennie ; Jolley, Jennifer ; Sager, Hendrik ; Bornstein, Stefan R. ; Schwarz, Peter E. H. ; Kristiansson, Kati ; Perola, Markus ; Lindström, Jaana ; Swift, Amy J. ; Uusitupa, Matti ; Atalay, Mustafa ; Lakka, Timo A. ; Rauramaa, Rainer ; Bolton, Jennifer L. ; Fowkes, Gerry ; Fraser, Ross M. ; Price, Jackie F. ; Fischer, Krista ; KrjutÅ¡kov, Kaarel ; Metspalu, Andres ; Mihailov, Evelin ; Langenberg, Claudia ; Luan, Jian'an ; Ong, Ken K. ; Chines, Peter S. ; Keinanen-Kiukaanniemi, Sirkka M. ; Saaristo, Timo E. ; Edkins, Sarah ; Franks, Paul W. ; Hallmans, Göran ; Shungin, Dmitry ; Morris, Andrew David ; Palmer, Colin N. A. ; Erbel, Raimund ; Moebus, Susanne ; Nöthen, Markus Maria ; Pechlivanis, Sonali ; Hveem, Kristian ; Narisu, Narisu ; Hamsten, Anders ; Humphries, Steve E. ; Strawbridge, Rona J. ; Tremoli, Elena ; Grallert, Harald ; Thorand, Barbara ; Illig, Thomas ; Koenig, Wolfgang ; Müller-Nurasyid, Martina ; Peters, Annette ; Böhm, Bernhard O. ; Kleber, Marcus E. ; März, Winfried ; Winkelmann, Bernhard R. ; Kuusisto, Johanna ; Laakso, Markku ; Arveiler, Dominique ; Cesana, Giancarlo ; Kuulasmaa, Kari ; Virtamo, Jarmo ; Yarnell, John W. G. ; Kuh, Diana ; Wong, Andrew ; Lind, Lars ; Faire, Ulf de ; Gigante, Bruna ; Magnusson, Patrik K. E. ; Pedersen, Nancy L. ; Dedoussis, George ; Dimitriou, Maria ; Kolovou, Genovefa ; Kanoni, Stavroula ; Stirrups, Kathleen ; Bonnycastle, Lori L. ; Njølstad, Inger ; Wilsgaard, Tom ; Ganna, Andrea ; Rehnberg, Emil ; Hingorani, Aroon ; Kivimaki, Mika ; Kumari, Meena ; Assimes, Themistocles L. ; Barroso, Inês ; Boehnke, Michael ; Borecki, Ingrid B. ; Deloukas, Panos ; Fox, Caroline S. ; Frayling, Timothy ; Groop, Leif C. ; Haritunians, Talin ; Hunter, David ; Ingelsson, Erik ; Kaplan, Robert ; Mohlke, Karen L. ; North, Kari E. ; Lindgren, Cecilia M. ; Qi, Lu ; Loos, Ruth J. F. ; Heid, Iris M. ; Hirschhorn, Joel N. ; McCarthy, Mark I. ; Abecasis, Gonçalo R. ; Stefansson, Kari ; Strachan, David P. ; Schlessinger, David ; O'Connell, Jeffrey R. ; Duijn, Cornelia M. van
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Hübner, Hanna ; Kurbacher, Christian M. ; Kuesters, Geoffrey ; Hartkopf, Andreas D. ; Lux, Michael Patrick ; Huober, Jens ; Volz, Bernhard ; Ţăran, Florin-Andrei ; Overkamp, Friedrich ; Tesch, Hans ; Häberle, Lothar ; Lüftner, Diana ; Wallwiener, Markus ; Müller, Volkmar ; Beckmann, Matthias Wilhelm ; Belleville, Erik ; Rübner, Matthias ; Untch, Michael ; Fasching, Peter Andreas ; Janni, Wolfgang ; Fehm, Tanja ; Kolberg, Hans-Christian ; Wallwiener, Diethelm ; Brucker, Sara Y. ; Schneeweiss, Andreas ; Ettl, Johannes
Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry.
Methods:Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor–positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria.
Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive.
Conclusion: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials.
Trial registration: Clinicaltrials, NCT02338167, Registered 14 January 2015 - retrospectively registered.
Lux, Michael Patrick ; Nabieva, Naiba ; Hartkopf, Andreas ; Huober, Jens ; Volz, Bernhard ; Ţăran, Florin-Andrei ; Overkamp, Friedrich ; Kolberg, Hans-Christian ; Hadji, Peyman ; Tesch, Hans ; Häberle, Lothar ; Ettl, Johannes ; Lüftner, Diana ; Wallwiener, Markus ; Müller, Volkmar ; Beckmann, Matthias Wilhelm ; Belleville, Erik ; Wimberger, Pauline ; Hielscher, Carsten ; Geberth, Matthias ; Abenhardt, Wolfgang ; Kurbacher, Christian M. ; Würstlein, Rachel ; Thomssen, Christoph ; Untch, Michael ; Fasching, Peter Andreas ; Janni, Wolfgang ; Fehm, Tanja ; Wallwiener, Diethelm ; Schneeweiss, Andreas ; Brucker, Sara
This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH → T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.
Wöckel, Achim ; Festl, Jasmin ; Stüber, Tanja ; Brust, Katharina ; Stangl, Stephanie ; Heuschmann, Peter Ulrich ; Albert, Ute Susann ; Budach, Wilfried ; Follmann, Markus ; Janni, Wolfgang ; Kopp, Ina ; Kreienberg, Rolf ; Kühn, Thorsten ; Langer, Thomas ; Nothacker, Monika ; Scharl, Anton ; Schreer, Ingrid ; Link, Hartmut ; Engel, Jutta ; Fehm, Tanja ; Weis, Joachim ; Welt, Anja ; Steckelberg, Anke ; Feyer, Petra ; König, Klaus ; Hahne, Andrea ; Kreipe, Hans H. ; Knoefel, Wolfram Trudo ; Denkinger, Michael ; Brucker, Sara ; Lüftner, Diana ; Kubisch, Christian ; Gerlach, Christina ; Lebeau, Annette ; Siedentopf, Friederike ; Petersen, Cordula ; Bartsch, Hans Helge ; Schulz-Wendtland, Rüdiger ; Hahn, Markus ; Hanf, Volker ; Müller-Schimpfle, Markus ; Henscher, Ulla ; Roncarati, Renza ; Katalinic, Alexander ; Heitmann, Christoph ; Honegger, Christoph ; Paradies, Kerstin ; Bjelic-Radisic, Vesna ; Degenhardt, Friedrich ; Wenz, Frederik ; Rick, Oliver ; Hölzel, Dieter ; Zaiss, Matthias ; Kemper, Gudrun ; Budach, Volker ; Denkert, Carsten Michael ; Gerber, Bernd ; Tesch, Hans ; Hirsmüller, Susanne ; Sinn, Hans-Peter ; Dunst, Jürgen ; Münstedt, Karsten ; Bick, Ulrich ; Fallenberg, Eva ; Tholen, Reina ; Hung, Roswita ; Baumann, Freerk T. ; Beckmann, Matthias Wilhelm ; Blohmer, Jens-Uwe ; Fasching, Peter Andreas ; Lux, Michael Patrick ; Harbeck, Nadia ; Hadji, Peyman ; Hauner, Hans ; Heywang-Köbrunner, Sylvia H. ; Huober, Jens ; Hübner, Jutta ; Jackisch, Christian ; Loibl, Sibylle ; Lück, Hans-Jürgen ; Minckwitz, Gunter von ; Möbus, Volker ; Müller, Volkmar ; Nöthlings, Ute ; Schmidt, Marcus ; Schmutzler, Rita Katharina ; Schneeweiss, Andreas ; Schütz, Florian ; Stickeler, Elmar ; Thomssen, Christoph ; Untch, Michael ; Wesselmann, Simone ; Bücker, Arno ; Krockenberger, Mathias Heinric
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
Wöckel, Achim ; Festl, Jasmin ; Stüber, Tanja ; Brust, Katharina ; Stangl, Stephanie ; Heuschmann, Peter Ulrich ; Albert, Ute Susann ; Budach, Wilfried ; Follmann, Markus ; Janni, Wolfgang ; Kopp, Ina ; Kreienberg, Rolf ; Kühn, Thorsten ; Langer, Thomas ; Nothacker, Monika ; Scharl, Anton ; Schreer, Ingrid ; Link, Hartmut ; Engel, Jutta ; Fehm, Tanja ; Weis, Joachim ; Welt, Anja ; Steckelberg, Anke ; Feyer, Petra ; König, Klaus ; Hahne, Andrea ; Kreipe, Hans H. ; Knoefel, Wolfram Trudo ; Denkinger, Michael ; Brucker, Sara ; Lüftner, Diana ; Kubisch, Christian ; Gerlach, Christina ; Lebeau, Annette ; Siedentopf, Friederike ; Petersen, Cordula ; Bartsch, Hans Helge ; Schulz-Wendtland, Rüdiger ; Hahn, Markus ; Hanf, Volker ; Müller-Schimpfle, Markus ; Henscher, Ulla ; Roncarati, Renza ; Katalinic, Alexander ; Heitmann, Christoph ; Honegger, Christoph ; Paradies, Kerstin ; Bjelic-Radisic, Vesna ; Degenhardt, Friedrich ; Wenz, Frederik ; Rick, Oliver ; Hölzel, Dieter ; Zaiss, Matthias ; Kemper, Gudrun ; Budach, Volker ; Denkert, Carsten Michael ; Gerber, Bernd ; Tesch, Hans ; Hirsmüller, Susanne ; Sinn, Hans-Peter ; Dunst, Jürgen ; Münstedt, Karsten ; Bick, Ulrich ; Fallenberg, Eva ; Tholen, Reina ; Hung, Roswita ; Baumann, Freerk T. ; Beckmann, Matthias Wilhelm ; Blohmer, Jens-Uwe ; Fasching, Peter Andreas ; Lux, Michael Patrick ; Harbeck, Nadia ; Hadji, Peyman ; Hauner, Hans ; Heywang-Köbrunner, Sylvia H. ; Huober, Jens ; Hübner, Jutta ; Jackisch, Christian ; Loibl, Sibylle ; Lück, Hans-Jürgen ; Minckwitz, Gunter von ; Möbus, Volker ; Müller, Volkmar ; Nöthlings, Ute ; Schmidt, Marcus ; Schmutzler, Rita Katharina ; Schneeweiss, Andreas ; Schütz, Florian ; Stickeler, Elmar ; Thomssen, Christoph ; Untch, Michael ; Wesselmann, Simone ; Bücker, Arno ; Krockenberger, Mathias Heinric
Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Beckmann, Christian ; Papazoglou, Panajotis ; Zschiesche, Detlef ; Schramm, Stefan ; Stöcker, Horst ; Greiner, Walter
A model based on chiral SU(3)-symmetry in nonlinear realisation is used for the investigation of nuclei, superheavy nuclei, hypernuclei and multistrange nuclear objects (so called MEMOs). The model works very well in the case of nuclei and hypernuclei with one Lambda-particle and rules out MEMOs. Basic observables which are known for nuclei and hypernuclei are reproduced satisfactorily. The model predicts Z=120 and N=172, 184 and 198 as the next shell closures in the region of superheavy nuclei. The calculations have been performed in self-consistent relativistic mean field approximation assuming spherical symmetry. The parameters were adapted to known nuclei.
Zschiesche, Detlef ; Papazoglou, Panajotis ; Beckmann, Christian W. ; Schramm, Stefan ; Schaffner-Bielich, Jürgen ; Stöcker, Horst ; Greiner, Walter
Introduction: Until now it is not possible to determine the equation of state (EOS) of hadronic matter from QCD. One succesfully applied alternative way to describe the hadronic world at high densities and temperatures are effective models like the RMF-models [1], where the relevant degrees of freedom are baryons and mesons instead of quarks and gluons. Since approximate chiral symmetry is an essential feature of QCD, it should be a useful concept for building and restricting e ective models. It has been shown [2,3] that effective sigma-omega models including SU(2) chiral symmetry are able to obtain a reasonable description of nuclear matter and finite nuclei. Recently [4] we have shown that an extended SU(3) × SU(3) chiral sigma-omega model is able to describe nuclear matter ground state properties, vacuum properties and finite nuclei satisfactorily. This model includes the lowest SU(3) multiplets of the baryons (octet and decuplet[5]), the spin-0 and the spin-1 mesons as the relevant degrees of freedom. Here we will discuss the predictions of this model for dense, hot, and strange hadronic matter.
Comics sind nicht linear, es gibt keine Vorgabe, ob wir zuerst die Bilder betrachten oder den Text lesen. So lassen die Brüche zwischen den Paneln, zwischen den Zeichen, zwischen den einzelnen Heften auch immer einen Raum entstehen. Einen Grenzraum, der verschiedene Lesarten und Fragen ermöglicht. Die dem Comic spezifische Ästhetik der Brüche und Wiederholungen wird im Comic 'Hure h' explizit benutzt, um Fragen nach Identität, Geschlechterrollen und Begehren aufzuwerfen und gesellschaftliche Zuschreibungen zu hinterfragen. Identität wird im Comic 'Hure h' nicht als feststehende Einheit dargestellt, sondern in ihrer fragmentierten Struktur gezeigt. Die Brüche in der Darstellung von Identität und die parodistische Bezugnahme auf gesellschaftliche Akte machen den Raum für eine Grenzüberschreitung der Geschlechternormen auf. Die Differenz zwischen den dargestellten Zeichen und deren imaginierten gesellschaftlichen Konnotationen lässt die Möglichkeit entstehen, dass Normvorstellungen und Konstruktionen von 'gender' und 'sex' als solche aufgezeigt und dadurch aufgebrochen werden.