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Pinto, Dalila ; Delaby, Elsa ; Merico, Daniele ; Barbosa, Mafalda ; Merikangas, Alison ; Klei, Lambertus ; Thiruvahindrapuram, Bhooma ; Xu, Xiao ; Ziman, Robert ; Wang, Zhuozhi ; Vorstman, Jacob A. S. ; Thompson, Ann P. ; Regan, Regina ; Pilorge, Marion ; Pellecchia, Giovanna ; Pagnamenta, Alistair T. ; Oliveira, Bárbara ; Marshall, Christian R. ; Magalhães, Tiago R. ; Lowe, Jennifer K. ; Howe, Jennifer L. ; Griswold, Anthony J. ; Gilbert, John ; Duketis, Eftichia ; Dombroski, Beth A. ; Jonge, Maretha de ; Cuccaro, Michael L. ; Crawford, Emily L. ; Correia, Catarina T. ; Conroy, Judith ; Conceição, Inȇs C. ; Geburtig-Chiocchetti, Andreas ; Casey, Jillian P. ; Cai, Guiqing ; Cabrol, Christelle ; Bolshakova, Nadia ; Bacchelli, Elena ; Anney, Richard ; Gallinger, Steven ; Cotterchio, Michelle ; Casey, Graham ; Zwaigenbaum, Lonnie ; Wittemeyer, Kerstin ; Wing, Kirsty ; Wallace, Simon ; Engeland, Herman van ; Tryfon, Ana ; Thomson, Susanne ; Soorya, Latha ; Roge, Bernadette ; Roberts, Wendy ; Poustka, Fritz ; Mouga, Susana ; Minshew, Nancy J. ; McInnes, L. Alison ; McGrew, Susan G. ; Lord, Catherine ; Leboyer, Marion ; Le Couteur, Ann ; Kolevzon, Alexander ; González, Patricia Jiménez ; Jacob, Suma ; Holt, Richard ; Guter, Stephen J. ; Green, Jonathan ; Green, Andrew ; Gillberg, Christopher ; Fernandez, Bridget A. ; Duque, Frederico ; Delorme, Richard ; Dawson, Geraldine ; Chaste, Pauline ; Café, Cátia ; Brennan, Sean ; Bourgeron, Thomas ; Bolton, Patrick F. ; Bölte, Sven ; Bernier, Raphael ; Baird, Gillian ; Bailey, Anthony J. ; Anagnostou, Evdokia ; Almeida, Joana ; Wijsman, Ellen M. ; Vieland, Veronica J. ; Vicente, Astrid M. ; Schellenberg, Gerard D. ; Pericak-Vance, Margaret Ann ; Paterson, Andrew D. ; Parr, Jeremy R. ; Oliveira, Guiomar ; Nurnberger, John I. ; Monaco, Anthony P. ; Maestrini, Elena ; Klauck, Sabine M. ; Hakonarson, Hakon ; Haines, Jonathan L. ; Geschwind, Daniel H. ; Freitag, Christine M. ; Folstein, Susan E. ; Ennis, Sean ; Coon, Hilary ; Battaglia, Agatino ; Szatmari, Peter ; Sutcliffe, James S. ; Hallmayer, Joachim ; Gill, Michael ; Cook, Edwin H. ; Buxbaum, Joseph D. ; Devlin, Bernie ; Gallagher, Louise ; Betancur, Catalina ; Scherer, Stephen W.
Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
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.
Weber, Heike ; Scholz, Claus Jürgen ; Domschke, Katharina ; Baumann, Christian ; Klauke, Benedikt ; Jacob, Christian P. ; Maier, Wolfgang ; Fritze, Jürgen ; Bandelow, Borwin ; Zwanzger, Peter M. ; Lang, Thomas ; Fehm, Lydia ; Ströhle, Andreas ; Hamm, Alfons ; Gerlach, Alexander ; Alpers, Georg W. ; Kircher, Tilo ; Wittchen, Hans-Ulrich ; Arolt, Volker ; Pauli, Paul ; Deckert, Jürgen ; Reif, Andreas
Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females.
Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score.
Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.
Casey, Jillian P. ; Magalhães, Tiago R. ; Conroy, Judith M. ; Regan, Regina ; Shah, Naisha ; Anney, Richard ; Shields, Denis C. ; Abrahams, Brett S. ; Almeida, Joana ; Bacchelli, Elena ; Bailey, Anthony J. ; Baird, Gillian ; Battaglia, Agatino ; Berney, Tom ; Bolshakova, Nadia ; Bolton, Patrick F. ; Bourgeron, Thomas ; Brennan, Sean ; Cali, Phil ; Correia, Catarina ; Corsello, Christina ; Coutanche, Marc ; Dawson, Geraldine ; Jonge, Maretha de ; Delorme, Richard ; Duketis, Eftichia ; Duque, Frederico ; Estes, Annette ; Farrar, Penny ; Fernandez, Bridget A. ; Folstein, Susan E. ; Foley, Suzanne ; Fombonne, Eric ; Freitag, Christine M. ; Gilbert, John ; Gillberg, Christopher ; Glessner, Joseph T. ; Green, Jonathan ; Guter, Stephen J. ; Hakonarson, Hakon ; Holt, Richard ; Hughes, Gillian ; Hus, Vanessa ; Igliozzi, Roberta ; Kim, Cecilia ; Klauck, Sabine M. ; Kolevzon, Alexander ; Lamb, Janine A. ; Leboyer, Marion ; Le Couteur, Ann ; Leventhal, Bennett L. ; Lord, Catherine ; Lund, Sabata C. ; Maestrini, Elena ; Mantoulan, Carine ; Marshall, Christian R. ; McConachie, Helen ; McDougle, Christopher J. ; McGrath, Jane ; McMahon, William M. ; Merikangas, Alison ; Miller, Judith ; Minopoli, Fiorella ; Mirza, Ghazala K. ; Munson, Jeff ; Nelson, Stanley F. ; Nygren, Gudrun ; Oliveira, Guiomar ; Pagnamenta, Alistair T. ; Papanikolaou, Katerina ; Parr, Jeremy R. ; Parrini, Barbara ; Pickles, Andrew ; Pinto, Dalila ; Piven, Joseph ; Posey, David J. ; Poustka, Annemarie ; Poustka, Fritz ; Ragoussis, Jiannis ; Roge, Bernadette ; Rutter, Michael L. ; Sequeira, Ana F. ; Soorya, Latha ; Sousa, Inês ; Sykes, Nuala ; Stoppioni, Vera ; Tancredi, Raffaella ; Tauber, Maïté ; Thompson, Ann P. ; Thomson, Susanne ; Tsiantis, John ; Engeland, Herman van ; Vincent, John B. ; Volkmar, Fred ; Vorstman, Jacob A. S. ; Wallace, Simon ; Wang, Kai ; Wassink, Thomas H. ; White, Kathy ; Wing, Kirsty ; Wittemeyer, Kerstin ; Yaspan, Brian L. ; Zwaigenbaum, Lonnie ; Betancur, Catalina ; Buxbaum, Joseph D. ; Cantor, Rita M. ; Cook, Edwin H. ; Coon, Hilary ; Cuccaro, Michael L. ; Geschwind, Daniel H. ; Haines, Jonathan L. ; Hallmayer, Joachim ; Monaco, Anthony P. ; Nurnberger, John I. ; Pericak-Vance, Margaret Ann ; Schellenberg, Gerard D. ; Scherer, Stephen W. ; Sutcliffe, James S. ; Szatmari, Peter ; Vieland, Veronica J. ; Wijsman, Ellen M. ; Green, Andrew ; Gill, Michael ; Gallagher, Louise ; Vicente, Astrid M. ; Ennis, Sean
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Werner, Volker ; Cooper, Nathan ; Goddard, Phil M. ; Humby, Peter ; Ilieva, Ralista S. ; Rusev, Gencho ; Beller, Jacob ; Bernards, Christian ; Crider, Benjamin P. ; Isaak, Johann ; Kelley, John H. ; Kwan, Elaine ; Löher, Bastian ; Peters, Erin E. ; Pietralla, Norbert ; Romig, Christopher ; Savran, Deniz ; Scheck, Marcus ; Tonchev, Anton P. ; Tornow, Werner ; Yates, Steven W. ; Zweidinger, Markus
A series of photon scattering experiments has been performed on the double-beta decay partners 76Ge and 76Se, in order to investigate their dipole response up to the neutron separation threshold. Gamma-ray beams from bremsstrahlung at the S-DALINAC and from Compton-backscattering at HIGS have been used to measure absolute cross sections and parities of dipole excited states, respectively. The HIGS data allows for indirect measurement of averaged branching ratios, which leads to significant corrections in the observed excitation cross sections. Results are compared to statistical calculations, to test photon strength functions and the Axel-Brink hypothesis.
Frieler, Katja ; Levermann, Anders ; Elliot, Joshua ; Heinke, Jens ; Arneth, Almut ; Bierkens, Marc F. P. ; Ciais, Philippe ; Clark, Douglas B. ; Deryng, Delphine ; Döll, Petra ; Falloon, Pete ; Fekete, Balázs M. ; Folberth, Christian ; Friend, Andrew D. ; Gellhorn, Catrin ; Gosling, Simon N. ; Haddeland, Ingjerd ; Khabarov, Nikolay ; Lomas, Marc R. ; Masaki, Yusuke ; Nishina, Kazuya ; Neumann, Kathleen ; Oki, Taikan ; Pavlick, Ryan ; Ruane, Alex C. ; Schmid, Erwin ; Schmitz, Christoph ; Stacke, Tobias ; Stehfest, Elke ; Tang, Qiuhong ; Wisser, Dominik ; Huber, Veronika ; Piontek, Franziska ; Warszawski, Lila ; Schewe, Jacob ; Lotze-Campen, Hermann ; Schellnhuber, Hans Joachim
Climate change and its impacts already pose considerable challenges for societies that will further increase with global warming (IPCC, 2014a, b). Uncertainties of the climatic response to greenhouse gas emissions include the potential passing of large-scale tipping points (e.g. Lenton et al., 2008; Levermann et al., 2012; Schellnhuber, 2010) and changes in extreme meteorological events (Field et al., 2012) with complex impacts on societies (Hallegatte et al., 2013). Thus climate change mitigation is considered a necessary societal response for avoiding uncontrollable impacts (Conference of the Parties, 2010). On the other hand, large-scale climate change mitigation itself implies fundamental changes in, for example, the global energy system. The associated challenges come on top of others that derive from equally important ethical imperatives like the fulfilment of increasing food demand that may draw on the same resources. For example, ensuring food security for a growing population may require an expansion of cropland, thereby reducing natural carbon sinks or the area available for bio-energy production. So far, available studies addressing this problem have relied on individual impact models, ignoring uncertainty in crop model and biome model projections. Here, we propose a probabilistic decision framework that allows for an evaluation of agricultural management and mitigation options in a multi-impact-model setting. Based on simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), we outline how cross-sectorally consistent multi-model impact simulations could be used to generate the information required for robust decision making.
Using an illustrative future land use pattern, we discuss the trade-off between potential gains in crop production and associated losses in natural carbon sinks in the new multiple crop- and biome-model setting. In addition, crop and water model simulations are combined to explore irrigation increases as one possible measure of agricultural intensification that could limit the expansion of cropland required in response to climate change and growing food demand. This example shows that current impact model uncertainties pose an important challenge to long-term mitigation planning and must not be ignored in long-term strategic decision making.
Frieler, Katja ; Levermann, Anders ; Elliot, Joshua ; Heinke, Jens ; Arneth, Almut ; Bierkens, Marc F. P. ; Ciais, Philippe ; Clark, Douglas B. ; Deryng, Delphine ; Döll, Petra ; Falloon, Pete ; Fekete, Balázs M. ; Folberth, Christian ; Friend, Andrew D. ; Gellhorn, Catrin ; Gosling, Simon N. ; Haddeland, Ingjerd ; Khabarov, Nikolay ; Lomas, Marc R. ; Masaki, Yusuke ; Nishina, Kazuya ; Neumann, Kathleen ; Oki, Taikan ; Pavlick, Ryan ; Ruane, Alex C. ; Schmid, Erwin ; Schmitz, Christoph ; Stacke, Tobias ; Stehfest, Elke ; Tang, Qiuhong ; Wisser, Dominik ; Huber, Veronika ; Piontek, Franziska ; Warszawski, Lila ; Schewe, Jacob ; Lotze-Campen, Hermann ; Schellnhuber, Hans Joachim
In order to achieve climate change mitigation, long-term decisions are required that must be reconciled with other societal goals that draw on the same resources. For example, ensuring food security for a growing population may require an expansion of crop land, thereby reducing natural carbon sinks or the area available for bio-energy production. Here, we show that current impact-model uncertainties pose an important challenge to long-term mitigation planning and propose a new risk-assessment and decision framework that accounts for competing interests.
Based on cross-sectorally consistent simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) we discuss potential gains and limitations of additional irrigation and trade-offs of the expansion of agricultural land as two possible response measures to climate change and growing food demand. We describe an illustrative example in which the combination of both measures may close the supply demand gap while leading to a loss of approximately half of all natural carbon sinks.
We highlight current limitations of available simulations and additional steps required for a comprehensive risk assessment.
Koning, Jos J. de ; Foster, Carl ; Bakkum, Arjan ; Kloppenburg, Sil ; Thiel, Christian ; Joseph, Trent ; Cohen, Jacob ; Porcari, John P.
Background: Athletic competition has been a source of interest to the scientific community for many years, as a surrogate of the limits of human ambulatory ability. One of the remarkable things about athletic competition is the observation that some athletes suddenly reduce their pace in the mid-portion of the race and drop back from their competitors. Alternatively, other athletes will perform great accelerations in mid-race (surges) or during the closing stages of the race (the endspurt). This observation fits well with recent evidence that muscular power output is regulated in an anticipatory way, designed to prevent unreasonably large homeostatic disturbances.
Principal Findings: Here we demonstrate that a simple index, the product of the momentary Rating of Perceived Exertion (RPE) and the fraction of race distance remaining, the Hazard Score, defines the likelihood that athletes will change their velocity during simulated competitions; and may effectively represent the language used to allow anticipatory regulation of muscle power output.
Conclusions: These data support the concept that the muscular power output during high intensity exercise performance is actively regulated in an anticipatory manner that accounts for both the momentary sensations the athlete is experiencing as well as the relative amount of a competition to be completed.
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