60 results on '"Alarcon-Riquelme ME"'
Search Results
2. Novel genes and sex differences in COVID-19 severity
- Author
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Cruz, R, Diz-de Almeida, S, de Heredia, ML, Quintela, I, Ceballos, FC, Lorenzo-Salazar, GM, Gonzalez-Montelongo, R, Gago-Dominguez, M, Porras, MS, Castano, JAT, Nevado, J, Aguado, JM, Aguilar, C, Aguilera-Albesa, S, Almadana, V, Almoguera, B, Alvarez, N, Andreu-Bernabeu, A, Arana-Arri, E, Arango, C, Arranz, MJ, Artiga, MJ, Baptista-Rosas, RC, Barreda-Sanchez, M, Belhassen-Garcia, M, Bezerra, JF, Bezerra, MAC, Boix-Palop, L, Brion, M, Brugada, R, Bustos, M, Calderon, EJ, Carbonell, C, Castano, L, Castelao, JE, Conde-Vicente, R, Cordero-Lorenzana, ML, Cortes-Sanchez, JL, Corton, M, Darnaude, MT, De Martino-Rodriguez, A, del Campo-Perez, V, de Bustamante, AD, Dominguez-Garrido, E, Luchessi, AD, Eiros, R, Sanabria, GME, Carmen Farinas, M, Fernandez-Robelo, U, Fernandez-Rodriguez, A, Fernandez-Villa, T, Gil-Fournier, B, Gomez-Arrue, J, Alvarez, BG, de Quiros, FGB, Gonzalez-Penas, J, Gutierrez-Bautista, JF, Herrero, MJ, Herrero-Gonzalez, A, Jimenez-Sousa, MA, Lattig, MC, Borja, AL, Lopez-Rodriguez, R, Mancebo, E, Martin-Lopez, C, Martin, V, Martinez-Nieto, O, Martinez-Lopez, I, Martinez-Resendez, MF, Martinez-Perez, A, Mazzeu, JF, Macias, EM, Minguez, P, Cuerda, VM, Silbiger, VN, Oliveira, SF, Ortega-Paino, E, Parellada, M, Paz-Artal, E, Santos, NPC, Perez-Matute, P, Perez, P, Perez-Tomas, ME, Perucho, T, Pinsach-Abuin, ML, Pompa-Mera, EN, Porras-Hurtado, GL, Pujol, A, Leon, SR, Resino, S, Fernandes, MR, Rodriguez-Ruiz, E, Rodriguez-Artalejo, F, Rodriguez-Garcia, JA, Cabello, FR, Ruiz-Hornillos, J, Ryan, P, Soria, JM, Souto, JC, Tamayo, E, Tamayo-Velasco, A, Taracido-Fernandez, JC, Teper, A, Torres-Tobar, L, Urioste, M, Valencia-Ramos, J, Yanez, Z, Zarate, R, Nakanishi, T, Pigazzini, S, Degenhardt, F, Butler-Laporte, G, Maya-Miles, D, Bujanda, L, Bouysran, Y, Palom, A, Ellinghaus, D, Martinez-Bueno, M, Rolker, S, Amitrano, S, Roade, L, Fava, F, Spinner, CD, Prati, D, Bernardo, D, Garcia, F, Darcis, G, Fernandez-Cadenas, I, Holter, JC, Banales, JM, Frithiof, R, Duga, S, Asselta, R, Pereira, AC, Romero-Gomez, M, Nafria-Jimenez, B, Hov, JR, Migeotte, I, Renieri, A, Planas, AM, Ludwig, KU, Buti, M, Rahmouni, S, Alarcon-Riquelme, ME, Schulte, EC, Franke, A, Karlsen, TH, Valenti, L, Zeberg, H, Richards, B, Ganna, A, Boada, M, de Rojas, I, Ruiz, A, Sanchez-Juan, P, Real, LM, Guillen-Navarro, E, Ayuso, C, Gonzalez-Neira, A, Riancho, JA, Rojas-Martinez, A, Flores, C, Lapunzina, P, and Carracedo, A
- Abstract
Here, we describe the results of a genome-wide study conducted in 11939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P= 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
- Published
- 2022
3. Mapping the human genetic architecture of COVID-19
- Author
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Niemi, MEK, Karjalainen, J, Liao, RG, Neale, BM, Daly, M, Ganna, A, Pathak, GA, Andrews, SJ, Kanai, M, Veerapen, K, Fernandez-Cadenas, I, Schulte, EC, Striano, P, Marttila, M, Minica, C, Marouli, E, Karim, MA, Wendt, FR, Savage, J, Sloofman, L, Butler-Laporte, G, Kim, H-N, Kanoni, S, Okada, Y, Byun, J, Han, Y, Uddin, MJ, Smith, GD, Willer, CJ, Buxbaum, JD, Mehtonen, J, Finucane, H, Cordioli, M, Martin, AR, Zhou, W, Pasaniuc, B, Julienne, H, Aschard, H, Shi, H, Yengo, L, Polimanti, R, Ghoussaini, M, Schwartzentruber, J, Dunham, I, Chwialkowska, K, Francescatto, M, Trankiem, A, Balaconis, MK, Davis, L, Lee, S, Priest, J, Renieri, A, Sankaran, VG, van Heel, D, Deelen, P, Richards, JB, Nakanishi, T, Biesecker, L, Kerchberger, VE, Kenneth, J, Mari, F, Bernasconi, A, Ceri, S, Canakoglu, A, Wolford, B, Faucon, A, Dutta, AK, Schurmann, C, Harry, E, Birney, E, Nguyen, H, Nasir, J, Kaunisto, M, Solomonson, M, Dueker, N, Vadgama, N, Limou, S, Rahmouni, S, Mbarek, H, Darwish, D, Uddin, MM, Albertos, R, Perez-Tur, J, Li, R, Folkersen, L, Moltke, I, Koelling, N, Teumer, A, Kousathanas, A, Utrilla, A, Verdugo, RA, Zarate, R, Medina-Gomez, C, Gomez-Cabrero, D, Carnero-Montoro, E, Cadilla, CL, Moreno-Estrada, A, Garmendia, A, Moya, L, Sedaghati-Khayat, B, Boua, PR, Fave, M-J, Francioli, L, Lemacon, A, Migeotte, I, Patel, S, Varnai, R, Szentpeteri, JL, Sipeky, C, Colombo, F, von Hohenstaufen, K, Lio, P, Vallerga, C, Wang, Q, Tanigawa, Y, Im, H, Han, C, Song, H, Lim, J, Lee, Y, Kim, S, Im, S, Atanasovska, B, Ahmad, HF, Boer, C, Jansen, P, Franke, L, Kaja, E, Pasko, D, Kennis-Szilagyi, I, Kornilov, SA, Prijatelj, V, Prokic, I, Sivanadhan, I, Perumal, S, Esmaeeli, S, Pearson, NM, Auton, A, Shelton, JF, Shastri, AJ, Filshtein-Sonmez, T, Coker, D, Symons, A, Esparza-Gordillo, J, Aslibekyan, S, O'Connell, J, Ye, C, Weldon, CH, Perera, M, O'Leary, K, Tuck, M, O'Brien, T, Meltzer, D, O'Donnell, P, Nutescu, E, Yang, G, Alarcon, C, Herrmann, S, Mazurek, S, Banagan, J, Hamidi, Z, Barbour, A, Raffat, N, Moreno, D, Friedman, P, Ferwerda, B, van de Beek, D, Brouwer, MC, Vlaar, APJ, Wiersinga, WJ, Posthuma, D, Tissink, E, Zwinderman, AHK, Uffelmann, E, van Agtmael, M, Algera, AG, van Baarle, F, Bax, D, Beudel, M, Bogaard, HJ, Bomers, M, Bonta, PI, Bos, L, Botta, M, de Brabander, J, de Bree, G, de Bruin, S, Bugiani, M, Bulle, E, Chouchane, O, Cloherty, A, Dongelmans, D, Elbers, P, Fleuren, L, Geerlings, S, Geerts, B, Geijtenbeek, T, Girbes, A, Goorhuis, B, Grobusch, MP, Hafkamp, F, Hagens, L, Hamann, J, Harris, V, Hemke, R, Hermans, SM, Heunks, L, Hollmann, M, Horn, J, Hovius, JW, de Jong, MD, Koning, R, van Mourik, N, Nellen, J, Nossent, EJ, Paulus, F, Peters, E, van der Poll, T, Preckel, B, Prins, JM, Raasveld, J, Reijnders, T, Schinkel, M, Schultz, MJ, Schuurman, A, Sigaloff, K, Smit, M, Stijnis, CS, Stilma, W, Teunissen, C, Thoral, P, Tsonas, A, van der Valk, M, Veelo, D, de Vries, H, van Vugt, M, Wouters, D, Minnaar, RP, Kromhout, A, van Uffelen, KWJ, Wolterman, RA, Roberts, G, Park, D, Ball, CA, Coignet, M, McCurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Hong, EL, Rand, K, Girshick, A, Guturu, H, Baltzell, AH, Guntz, J, Beguin, Y, Pigazzini, S, Nkambule, L, Bouysran, Y, Busson, A, Peyrassol, X, Wilkin, F, Pichon, B, Smits, G, Vandernoot, I, Goffard, J-C, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Jadot, L, Azarzar, S, Dellot, P, Gofflot, S, Claassen, S, Bertrand, A, Parzibut, G, Clarinval, M, Moermans, C, Malaise, O, El Kandoussi, K, Thonon, R, Huynen, P, Mesdagh, A, Melo, S, Jacques, N, Di Valentin, E, Giroule, F, Collignon, A, Radermecker, C, Lebrun, M, Peree, H, Latour, S, Barada, O, Sanchez, J, Josse, C, Boujemla, B, Meunier, M, Mariavelle, E, Anania, S, Gazon, H, Juszczak, D, Fadeur, M, Camby, S, Meuris, C, Thys, M, Jacques, J, Henket, M, Leonard, P, Frippiat, F, Giot, J-B, Sauvage, A-S, Von Frenckell, C, Mni, M, Wery, M, Staderoli, A, Belhaj, Y, Lambermont, B, Morrison, DR, Mooser, V, Forgetta, V, Ghosh, B, Laurent, L, Belisle, A, Henry, D, Abdullah, T, Adeleye, O, Mamlouk, N, Kimchi, N, Afrasiabi, Z, Rezk, N, Vulesevic, B, Bouab, M, Guzman, C, Petitjean, L, Tselios, C, Xue, X, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Brassard, N, Durand, M, Schurr, E, Lepage, P, Ragoussis, J, Auld, D, Chasse, M, Kaufmann, DE, Lathrop, GM, Adra, D, Davis, LK, Cox, NJ, Below, JE, Sealock, JM, Faucon, AB, Shuey, MM, Polikowsky, HG, Petty, LE, Shaw, DM, Chen, H-H, Zhu, W, Ludwig, KU, Schroeder, J, Maj, C, Rolker, S, Noethen, MM, Fazaal, J, Keitel, V, Jensen, B-EO, Feldt, T, Kurth, I, Marx, N, Dreher, M, Pink, I, Cornberg, M, Illig, T, Lehmann, C, Schommers, P, Augustin, M, Rybniker, J, Knopp, L, Eggermann, T, Volland, S, Altmueller, J, Berger, MM, Brenner, T, Hinney, A, Witzke, O, Bals, R, Herr, C, Ludwig, N, Walter, J, Fuchsberger, C, Pattaro, C, De Grandi, A, Pramstaller, P, Emmert, D, Melotti, R, Foco, L, Mascalzoni, D, Gogele, M, Domingues, F, Hicks, A, Gignoux, CR, Wicks, SJ, Crooks, K, Barnes, KC, Daya, M, Shortt, J, Rafaels, N, Chavan, S, Goldstein, DB, Kiryluk, K, Sengupta, S, Chung, W, Reilly, MP, Khan, A, Wang, C, Povysil, G, Bhardwaj, N, Gharavi, AG, Ionita-Laza, I, Shang, N, O'Byrne, SM, Nandakumar, R, Menon, A, So, YS, Hod, E, Pendrick, D, Park, S-K, Kim, H-L, Kang, CK, Lee, H-J, Song, K-H, Yoon, KJ, Paik, N-J, Seok, W, Yoon, H, Joo, E-J, Chang, Y, Ryu, S, Park, WB, Park, JS, Park, KU, Ham, SY, Jung, J, Kim, ES, Kim, HB, Ellinghaus, D, Degenhardt, F, Caceres, M, Juzenas, S, Lenz, TL, Albillos, A, Julia, A, Heidecker, B, Garcia, F, Kurth, F, Tran, F, Hanses, F, Zoller, H, Holter, JC, Fernandez, J, Sander, LE, Rosenstiel, P, Koehler, P, de Cid, R, Asselta, R, Schreiber, S, Hehr, U, Prati, D, Baselli, G, Valenti, L, Bujanda, L, Banales, JM, Duga, S, D'Amato, M, Romero-Gomez, M, Buti, M, Invernizzi, P, Franke, A, Hov, JR, Karlsen, TH, Folseraas, T, Maya-Miles, D, Teles, A, Azuure, C, Wacker, EM, Uellendahl-Werth, F, Elabd, H, Arora, J, Lerga-Jaso, J, Wienbrandt, L, Ruehlemann, MC, Wendorff, M, Vadla, MS, Lenning, OB, Oezer, O, Myhre, R, Raychaudhuri, S, Tanck, A, Gassner, C, Hemmrich-Stanisak, G, Kaessens, J, Basso, MEF, Schulzky, M, Wittig, M, Braun, N, Wesse, T, Albrecht, W, Yi, X, Ortiz, AB, Garrido Chercoles, A, Ruiz, A, Mantovani, A, Holten, AR, Mayer, A, Cherubini, A, Protti, A, Aghemo, A, Gerussi, A, Ramirez, A, Braun, A, Barreira, A, Lleo, A, Kildal, AB, Glueck, A, Carreras Nolla, A, Latiano, A, Dyrhol-Riise, AM, Muscatello, A, Voza, A, Rando-Segura, A, Solier, A, Karina, B, Cortes, B, Mateos, B, Nafria-Jimenez, B, Schaefer, B, Bellinghausen, C, Ferrando, C, Quereda, C, Skurk, C, Thibeault, C, Spinner, CD, Lange, C, Hu, C, Cappadona, C, Bianco, C, Sancho, C, Hoff, DAL, Galimberti, D, Jimenez, D, Pestana, D, Toapanta, D, Azzolini, E, Scarpini, E, Helbig, ET, Urrechaga, E, Paraboschi, EM, Pontali, E, Reverter, E, Navas, E, Arana, E, Garcia Sanchez, F, Ceriotti, F, Malvestiti, F, Mesonero, F, Pezzoli, G, Lamorte, G, Neb, H, My, I, Hernandez, I, de Rojas, I, Galvan-Femenia, I, Heyckendorf, J, Badia, JR, Schneider, J, Goikoetxea, J, Kraft, J, Mueller, KE, Gaede, KI, Garcia-Etxebarria, K, Tonby, K, Heggelund, L, Izquierdo-Sanchez, L, Sumoy, L, Lippert, LJ, Terranova, L, Garbarino, L, Tellez, L, Roade, L, Ostadreza, M, Intxausti, M, Kogevinas, M, Gutierrez-Stampa, MA, Vehreschild, MJGT, Marquie, M, Castoldi, M, Cecconi, M, Boada, M, Seilmaier, MJ, Mazzocco, M, Rodriguez-Gandia, M, Imaz Ayo, N, Blay, N, Martinez, N, Cornely, OA, Palmieri, O, Tentorio, P, Rodrigues, PM, Espana, PP, Hoffmann, P, Bacher, P, Suwalski, P, de Pablo, R, Nieto, R, Badalamenti, S, Ciesek, S, Bombace, S, Wilfling, S, Brunak, S, Heilmann-Heimbach, S, Ripke, S, Bahmer, T, Landmesser, U, Protzer, U, Rimoldi, V, Skogen, V, Andrade, V, Moreno, V, Poller, W, Farre, X, Wang, X, Khodamoradi, Y, Karadeniz, Z, de Salazar, A, Palom, A, Garcia-Fernandez, A-E, Blanco-Grau, A, Zanella, A, Bandera, A, Nebel, A, Biondi, A, Caba Llero-Garralda, A, Gori, A, Lind, A, Fracanzani, AL, Peschuck, A, Pesenti, A, De la Horra, C, Milani, C, Paccapelo, C, Angelini, C, Cea, C, Muniz-Diaz, E, Sandoval, E, Calderon, EJ, Solligard, E, Aziz, F, Martinelli-Boneschi, F, Peyvandi, F, Blasi, F, Medrano, FJ, Rodriguez-Frias, F, Mueller, F, Grasselli, G, Costantino, G, Cardamone, G, Foti, G, Matullo, G, Kurihara, H, Afset, JE, Damas, JK, Ampuero, J, Martin, J, Erdmann, J, Bergan, J, Goerg, S, Ferrusquia-Acosta, J, Hernandez Quero, J, Delgado, J, Guerrero, JM, Risnes, K, Bettini, LR, Moreira, L, Gustad, LT, Santoro, L, Scudeller, L, Riveiro-Barciela, M, Schaefer, M, Carrabba, M, Valsecchi, MG, Hernandez-Tejero, M, Acosta-Herrera, M, D'Angio, M, Baldini, M, Cazzaniga, M, Ciccarelli, M, Bocciolone, M, Miozzo, M, Chueca, N, Montano, N, Faverio, P, Preatoni, P, Bonfanti, P, Omodei, P, Castro, P, Ferrer, R, Gualtierotti, R, Gallego-Duran, R, Morilla, R, Haider, S, Marsal, S, Aneli, S, Pelusi, S, Bosari, S, Aliberti, S, Dudman, S, Zheng, T, Pumarola, T, Gonzalez Cejudo, T, Monzani, V, Friaza, V, Peter, W, Dopazo, X, May, S, Grimsrud, MM, Gudbjartsson, DF, Stefansson, K, Sulem, P, Sveinbjornsson, G, Melsted, P, Norddahl, G, Moore, KHS, Thorsteinsdottir, U, Holm, H, Alarcon-Riquelme, ME, Bernardo, D, Martinez-Bueno, M, Rojo Rello, S, Magi, R, Milani, L, Metspalu, A, Laisk, T, Lall, K, Lepamets, M, Esko, T, Reimann, E, Naaber, P, Laane, E, Pesukova, J, Peterson, P, Kisand, K, Tabri, J, Allos, R, Hensen, K, Starkopf, J, Ringmets, I, Tamm, A, Kallaste, A, Alavere, H, Metsalu, K, Puusepp, M, Kristiansson, K, Koskelainen, S, Perola, M, Donner, K, Kivinen, K, Palotie, A, Rivolta, C, Bochud, P-Y, Bibert, S, Boillat, N, Nussle, SG, Albrich, W, Quinodoz, M, Kamdar, D, Suh, N, Neofytos, D, Erard, V, Voide, C, Bochud, PY, Friolet, R, Vollenweider, P, Pagani, JL, Oddo, M, zu Bentrup, FM, Conen, A, Clerc, O, Marchetti, O, Guillet, A, Guyat-Jacques, C, Foucras, S, Rime, M, Chassot, J, Jaquet, M, Viollet, RM, Lannepoudenx, Y, Portopena, L, Desgranges, F, Filippidis, P, Guery, B, Haefliger, D, Kampouri, EE, Manuel, O, Munting, A, Iou-Olivgeris, MP, Regina, J, Rochat-Stettler, L, Suttels, V, Tadini, E, Tschopp, J, Van Singer, M, Viala, B, Boillat-Blanco, N, Brahier, T, Hugli, O, Meuwly, JY, Pantet, O, Bochud, M, D'Acremont, V, Younes, SE, Albrich, WC, Cerny, A, O'Mahony, L, von Mering, C, Frischknecht, M, Kleger, G-R, Filipovic, M, Kahlert, CR, Wozniak, H, Negro, TR, Pugin, J, Bouras, K, Knapp, C, Egger, T, Perret, A, Montillier, P, di Bartolomeo, C, Barda, B, Carreras, A, Mercader, JM, Guindo-Martinez, M, Torrents, D, Garcia-Aymerich, J, Castano-Vinyals, G, Dobano, C, Gori, M, Mondelli, MU, Castelli, F, Vaghi, M, Rusconi, S, Montagnani, F, Bargagli, E, Franchi, F, Mazzei, MA, Cantarini, L, Tacconi, D, Feri, M, Scala, R, Spargi, G, Nencioni, C, Bandini, M, Caldarelli, GP, Spagnesi, M, Canaccini, A, Ognibene, A, Monforte, AD, Girardis, M, Antinori, A, Francisci, D, Schiaroli, 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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, 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., Zöllner, Sebastian, Wang, Jiongming, Beck, Andrew, Sloofman, Laura G., Ascolillo, Steven, Sebra, Robert P., Collins, Brett L., Levy, Te, 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, Avromie, 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, Ari, 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-Françoi, 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, Jani, Rovite, Vita, Rescenko, Raimond, Peculis, Raiti, Ustinova, Monta, Zeberg, Hugo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Johnson, Ruth, Geschwind, Daniel H., Freimer, Nelson, Butte, Manish J., Ding, Yi, Chiu, Alec, Chang, Timothy S., Boutros, Paul, Moutsianas, Louka, 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., Tsuo, Kristin, Baya, Nikola, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Seed, Cotton, Daly, Mark J., Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicola, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, 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, Nichola, 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, Chri, 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, Larkin, Susan, Leiner, Tama, Lillie, Patrick, Limb, Jame, Linnett, Vanessa, Little, Jeff, Lyttle, Mark, Macmahon, Michael, Macnaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, Mccullough, Katherine, Mcewen, Ruth, Meda, Manjula, Mills, Gary H., Minton, Jane, Ward, Karl, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, Jame, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapa, Nelson, Mark, O’Shea, Matthew K., Otahal, Igor, Ostermann, Marlie, Pais, Mark, Panchatsharam, Selva, Papakonstantinou, Danai, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Pooni, Jagtur Singh, Post, Frank, Price, David, Prout, Rachel, Rae, Nikola, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ryan, Brendan, Saluja, Taranprit, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tama, Tatham, Kate, Thomas, Jo, Thompson, Chri, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Ustianowski, Andrew, Vallotton, Nick, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Papineni, Padmasayee, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Cole, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wooton, Daniel G., Workman, Andrew, Yates, Bryan, Young, Peter, Beale, Rupert, Bretherick, Andrew D., Clohisey, Sara, Fourman, Max Head, Furniss, Jame, Gountouna, Elvina, Grimes, Graeme, Haley, Chri, Harrison, David, Hayward, Caroline, Keating, Sean, Klaric, Lucija, Klenerman, Paul, Law, Andy, Meynert, Alison M., Millar, Jonathan, Pairo-Castineira, Erola, Parkinson, Nichola, Ponting, Chris P., Porteous, David J., Rawlik, Konrad, Richmond, Anne, Rowan, Kathy, Russell, Clark D., Shen, Xia, Shih, Barbara, Tenesa, Albert, Vitart, Veronique, Wang, Bo, Wilson, James F., Wu, Yang, Yang, Jian, Yang, Zhijian, Zechner, Marie, Zhai, Ranran, Zheng, Chenqing, Norman, Lisa, Pius, Riinu, Drake, Thomas M., Fairfield, Cameron J., Knight, Stephen R., Mclean, Kenneth A., Murphy, Derek, Shaw, Catherine A., Dalton, Jo, Girvan, Michelle, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Leeming, Gary, Law, Andrew, Wham, Murray, Hendry, Ro, Scott-Brown, Jame, Begg, Colin, Hinds, Charle, Wai Ho, Antonia Ying, Horby, Peter W., Knight, Julian, Ling, Lowell, Maslove, David, Mcauley, Danny, Montgomery, Hugh, Nichol, Alistair, Openshaw, Peter J. M., Summers, Charlotte, Walsh, Timothy, Armstrong, Lisa, Bates, Hayley, Dooks, Emma, Farquhar, Fiona, Hairsine, Brigid, Mcparland, C., Packham, Sophie, Alldis, Zoe, Astin-Chamberlain, Raine, Bibi, Fatima, Biddle, Jack, Blow, Sarah, Bolton, Matthew, Borra, Catherine, Bowles, Ruth, Burton, Maudrian, Choudhury, Yasmin, Collier, David, Cox, Amber, Easthope, Amy, Ebano, Patrizia, Fotiadis, Stavro, Gurasashvili, Jana, Halls, Rosslyn, Hartridge, Pippa, Kallon, Delordson, Kassam, Jamila, Lancoma-Malcolm, Ivone, Matharu, Maninderpal, May, Peter, Mitchelmore, Oliver, Newman, Tabitha, Patel, Mital, Pheby, Jane, Pinzuti, Irene, Prime, Zoe, Prysyazhna, Oleksandra, Shiel, Julian, Taylor, Melanie, Tierney, Carey, Wood, Suzanne, Zak, Anne, Zongo, Olivier, Forsey, Miranda, Nicholson, Anne, Riches, Joanne, Vertue, Mark, Wasson, Christopher, Finn, Stephanie, Green, Jackie, Collins, Erin, King, Bernadette, Grauslyte, Lina, Hussain, Musarat, Pogreban, Tatiana, Rosaroso, Lace, Salciute, Erika, Franke, George, Wong, Joanna, George, Aparna, Akeroyd, Louise, Bano, Shereen, Bromley, Matt, Gurr, Lucy, Lawton, Tom, Morgan, Jame, Sellick, Kirsten, Warren, Deborah, Wilkinson, Brian, Mcgowan, Janet, Ledgard, Camilla, Stacey, Amelia, Pye, Kate, Bellwood, Ruth, Bentley, Michael, Loosley, Ronda, Mcguinness, Heather, Tench, Helen, Wolf-Roberts, Rebecca, Gibson, Sian, Lyle, Amanda, Mcneela, Fiona, Radhakrishnan, Jayachandran, Hughes, Alistair, Ali, Asifa, Brady, Megan, Dale, Sam, Dance, Annalisa, Gledhill, Lisa, Greig, Jill, Hanson, Kathryn, Holdroyd, Kelly, Home, Marie, Kelly, Diane, Kitson, Ro, Matapure, Lear, Melia, Deborah, Mellor, Samantha, Nortcliffe, Tonicha, Pinnell, Jez, Robinson, Matthew, Shaw, Lisa, Shaw, Ryan, Thomis, Lesley, Wilson, Alison, Wood, Tracy, Bayo, Lee-Ann, Merwaha, Ekta, Ishaq, Tahira, Hanley, Sarah, Antcliffe, David, Banach, Dorota, Brett, Stephen, Coghlan, Phoebe, Fernandez, Ziortza, Gordon, Anthony, Rojo, Roceld, Arias, Sonia Sousa, Templeton, Maie, Jha, Rajeev, Krishnamurthy, Vinodh, Lim, Lai, Bi, Rehana, Scholefield, Barney, Ashton, Lydia, Williams, Alison, Cheyne, Claire, Saunderson, Anne, Allan, Angela, Anderson, Felicity, Kaye, Callum, Liew, Jade, Medhora, Jasmine, Scott, Teresa, Trumper, Erin, Botello, Adriana, Polgarova, Petra, Stroud, Katerina, Meaney, Eoghan, Jones, Megan, Ng, Anthony, Agrawal, Shruti, Pathan, Nazima, White, Deborah, Daubney, Esther, Elston, Kay, Parker, Robert, Reddy, Amie, Turner-Bone, Ian, Wilding, Laura, Harding, Peter, Jacob, Reni, Jones, Cathy, Denmade, Craig, Croft, Maria, White, Ian, Lim, Li, Griffin, Denise, Muchenje, Nycola, Mupudzi, Mcdonald, Partridge, Richard, Conyngham, Jo-Anna, Thomas, Rachel, Wright, Mary, Corral, Maria Alvarez, Bastion, Victoria, Clarke, Daphene, David, Beena, Kent, Harriet, Lorusso, Rachel, Lubimbi, Gamu, Murdoch, Sophie, Penacerrada, Melchizedek, Thomas, Alastair, Valentine, Jennifer, Vochin, Ana, Wulandari, Retno, Djeugam, Brice, Dawson, Joy, Garrioch, Sweyn, Tolson, Melanie, Aldridge, Jonathan, de Almeida Martins, Laura Gome, Carungcong, Jaime, Beavis, Sarah, Dale, Katie, Gascoyne, Rachel, Hawes, Joanne, Pritchard, Kelly, Stevenson, Lesley, Whileman, Amanda, Cowley, Anne, Highgate, Judith, Crawley, Rikki, Crew, Abigail, Cunningham, Mishell, Daniels, Allison, Harrison, Laura, Hope, Susan, Inweregbu, Ken, Jones, Sian, Lancaster, Nicola, Matthews, Jamie, Nicholson, Alice, Wray, Gemma, Benham, Leonie, Bradshaw, Zena, Brown, Joanna, Caswell, Melanie, Melling, Sarah, Preston, Stephen, Slawson, Nicola, Stoddard, Emma, Warden, Scott, Combes, Edward, Joefield, Teishel, Monnery, Sonja, Beech, Valerie, Trotman, Sallyanne, Hopkins, Bridget, Scriven, Jame, Thrasyvoulou, Laura, Willis, Heather, Anderson, Susan, Birch, Janine, Collins, Emma, Hammerton, Kate, O’Leary, Ryan, Abernathy, Caroline, Foster, Louise, Gratrix, Andrew, Martinson, Vicky, Parkinson, Priyai, Stones, Elizabeth, Carbral-Ortega, Llucia, Kapoor, Ritoo, Loader, David, Castle, Karen, Brandwood, Craig, Smith, Lara, Clark, Richard, Birchall, Katie, Kolakaluri, Laurel, Baines, Deborah, Sukumaran, Anila, Mapfunde, Isheunesu, Meredith, Megan, Morris, Lucy, Ryan, Lucy, Clark, Amy, Sampson, Julia, Peters, Cecilia, Dent, Martin, Langley, Margaret, Ashraf, Saima, Wei, Shuying, Andrew, Angela, Chablani, Manish, Kirkby, Amy, Netherton, Kimberley, Bates, Michelle, Dasgin, Jo, Gill, Jaspret, Nilsson, Annette, Apetri, Elena, Basikolo, Cathrine, Blackledge, Bethan, Catlow, Laura, Charles, Bethan, Doonan, Reece, Harris, Jade, Harvey, Alice, Horner, Daniel, Knowles, Karen, Lee, Stephanie, Lomas, Diane, Lyons, Chloe, Marsden, Tracy, Mclaughlan, Danielle, Mcmorrow, Liam, Pendlebury, Jessica, Perez, Jane, Poulaka, Maria, Proudfoot, Nicola, Slaughter, Melanie, Slevin, Kathryn, Thomas, Vicky, Walker, Danielle, Michael, Angiy, Collis, Matthew, Clark, Martyn, Coulding, Martina, Jude, Edward, Mccormick, Jacqueline, Mercer, Oliver, Potla, Darsh, Rehman, Hafiz, Savill, Heather, Turner, Victoria, Davey, Miriam, Golden, David, Seaman, Rebecca, Hunt, Jodie, Dearden, Joy, Dobson, Emma, Mulcahy, Michelle, Munt, Sheila, O’Connor, Grainne, Philbin, Jennifer, Rishton, Chloe, Tully, Redmond, Winnard, Sarah, Cagova, Lenka, Fofano, Adama, Garner, Lucie, Holcombe, Helen, Mepham, Sue, Mitchell, Alice Michael, Mwaura, Lucy, Praman, K., Vuylsteke, Alain, Zamikula, Julie, Bercades, Georgia, Brealey, David, Hass, Ingrid, Maccallum, Niall, Martir, Glady, Raith, Eamon, Reyes, Anna, Smyth, Deborah, Taylor, Abigail, Hughes, Rachel Anne, Thomas, Helen, Rees, Alun, Duskova, Michaela, Phipps, Janet, Brooks, Suzanne, Edwards, Michelle, Alexander, Peter, Allen, Schvearn, Bradley-Potts, Joanne, Brantwood, Craig, Egan, Jasmine, Felton, Timothy, Padden, Grace, Ward, Luke, Moss, Stuart, Glasgow, Susannah, Beesley, Kate, Board, Sarah, Kubisz-Pudelko, Agnieszka, Lewis, Alison, Perry, Je, Pippard, Lucy, Wood, Di, Buckley, Clare, Brown, Alison, Gregory, Jane, O’Connell, Susan, Smith, Tim, Belagodu, Zakaula, Fuller, Bridget, Gherman, Anca, Olufuwa, Olumide, Paramsothy, Remi, Stuart, Carmel, Oakley, Naomi, Kamundi, Charlotte, Tyl, David, Collins, Katy, Silva, Pedro, Taylor, June, King, Laura, Coates, Charlotte, Crowley, Maria, Wakefield, Phillipa, Beadle, Jane, Johnson, Laura, Sargeant, Janet, Anderson, Madeleine, Jardine, Catherine, Williams, Dewi, Parris, Victoria, Quaid, Sheena, Watson, Ekaterina, Melville, Julie, Naisbitt, Jay, Joseph, Rosane, Lazo, Maria, Walton, Olivia, Neal, Alan, Hill, Michaela, Kannan, Thogulava, Wild, Laura, Allan, Elizabeth, Darlington, Kate, Davies, Ffyon, Easton, Jack, Kumar, Sumit, Lean, Richard, Menzies, Daniel, Pugh, Richard, Qiu, Xinyi, Davies, Llino, Williams, Hannah, Scanlon, Jeremy, Davies, Gwyneth, Mackay, Callum, Lewis, Joannne, Rees, Stephanie, Coetzee, Samantha, Gales, Alistair, Raj, Meena, Sell, Craig, Langton, Helen, Watters, Malcolm, Novis, Catherine, Arbane, Gill, Bociek, Aneta, Campos, Sara, Grau, Neu, Jones, Tim Owen, Lim, Rosario, Marotti, Martina, Whitton, Christopher, Barron, Anthony, Collins, Ciara, Kaul, Sundeep, Passmore, Heather, Prendergast, Claire, Reed, Anna, Rogers, Paula, Shokkar, Rajvinder, Woodruff, Meriel, Middleton, Hayley, Polgar, Oliver, Nolan, Claire, Thwaites, Vicky, Mahay, Kanta, Sri-Chandana, Chunda, Scherewode, Joslan, Stephenson, Lorraine, Marsh, Sarah, Bancroft, Hollie, Bellamy, Mary, Carmody, Margaret, Daglish, Jacqueline, Moore, Faye, Rhodes, Joanne, Sangombe, Mirriam, Kadiri, Salma, Ayers, Amanda, Harrison, Wendy, North, Julie, Cavazza, Anna, Cockrell, Maeve, Corcoran, Eleanor, Depante, Maria, Finney, Clare, Jerome, Ellen, Mcphail, Mark, Nayak, Monalisa, Noble, Harriet, O’Reilly, Kevin, Pappa, Evita, Saha, Rohit, Saha, Sian, Smith, John, Knighton, Abigail, Gill, Mandy, Paul, Paul, Ratnam, Valli, Shelton, Sarah, Wynter, Inez, Baptista, David, Crowe, Rebecca, Fernandes, Rita, Herdman-Grant, Rosaleen, Joseph, Anna, Loveridge, Adam, Mckenley, India, Morino, Eriko, Naranjo, Andre, Simms, Richard, Sollesta, Kathryn, Swain, Andrew, Venkatesh, Harish, Khera, Jacyntha, Fox, Jonathan, Barber, Russell, Hewitt, Claire, Hilldrith, Annette, Jackson-Lawrence, Karen, Shepardson, Sarah, Wills, Maryanne, Butler, Susan, Tavares, Silvia, Cunningham, Amy, Hindale, Julia, Arif, Sarwat, George, Linsha, Twiss, Sophie, Wright, David, Holland, Maureen, Keenan, Natalie, Lyons, Marc, Wassall, Helen, Marsh, Chri, Mahenthran, Mervin, Carter, Emma, Kong, Thoma, Adanini, Oluronke, Bhatia, Nikhil, Msiska, Maine, Mew, Louise, Mwaura, Esther, Williams, Felicity, Wren, Lynn, Sutherland, Sara-Beth, Battle, Ceri, Brinkworth, Elaine, Harford, Rachel, Murphy, Carl, Newey, Luke, Rees, Tabitha, Williams, Marie, Arnold, Sophie, Hardy, John, Houlden, Henry, Moncur, Eleanor, Tariq, Ambreen, Tucci, Arianna, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Keshet-Price, Jocelyn, Randell, Georgina, Stammers, Katie, Abdelrazik, Marwa, Bakthavatsalam, Dhanalakshmi, Elhassan, Munzir, Ganesan, Arunkumar, Haldeos, Anne, Moreno-Cuesta, Jeronimo, Purohit, Dharam, Vincent, Rachel, Xavier, Kugan, Rohit, Kumar, Alasdair, Frater, Saleem, Malik, David, Carter, Jenkins, Samuel, Lamond, Zoe, Wall, Alanna, Reynolds, Jessica, Campbell, Helen, Thompsom, Maria, Dodds, Steve, Duffy, Stacey, Butcher, Deborah, O’Sullivan, Susie, Butterworth-Cowin, Nicola, Deacon, Bethan, Hibbert, Meg, Pothecary, Carla, Tetla, Dariusz, Woodford, Christopher, Durga, Latha, Kennard-Holden, Gareth, de Gordoa, Laura Ortiz-Ruiz, Peasgood, Emily, Phillips, Claire, Skinner, Denise, Gaylard, Jane, Mullan, Dee, Newman, Julie, Davies, Ellie, Roche, Lisa, Sathe, Sonia, Brimfield, Lutece, Daly, Zoe, Pogson, David, Rose, Steve, Collins, Amy, Khaliq, Waqa, Gude, Estefania Treu, Allen, Louise, Beranova, Eva, Crisp, Nikki, Deery, Joanne, Hazelton, Tracy, Knight, Alicia, Price, Carly, Tilbey, Sorrell, Turki, Salah, Turney, Sharon, Giles, Julian, Booth, Simon, Bell, Gillian, English, Katy, Katary, Amro, Wilcox, Louise, Campbell, Rachael, Clarke, Noreen, Whiteside, Jonathan, Mascarenhas, Mairi, Donaldson, Avril, Matheson, Joanna, Barrett, Fiona, O’Hara, Marianne, O’Keefe, Laura, Bradley, Clare, Collier, Dawn, Walker, Rachel, Maynard, Victoria, Patel, Tahera, Smith, Matthew, Kazi, Aayesha, Hartley, Janice, Dykes, Joseph, Hijazi, Muhammad, Keith, Sarah, Khan, Meherunnisa, Ryan-Smith, Janet, Springle, Philippa, Thomas, Jacqueline, Truman, Nick, Saad, Samuel, Coleman, Dabheoc, Fine, Christopher, Matt, Roseanna, Gay, Bethan, Dalziel, Jack, Ali, Syamlan, Goodchild, Drew, Harling, Rhiannan, Bhatterjee, Ravi, Goddard, Wendy, Davison, Chloe, Duberly, Stephen, Hargreaves, Jeanette, Bolton, Rachel, Verlander, Mark, Williams, Alexandra, Blackman, Helen, Creagh-Brown, Ben, Donlon, Sinead, Michalak-Glinska, Natalia, Mtuwa, Sheila, Pristopan, Veronika, Salberg, Armorel, Smith, Eleanor, Stone, Sarah, Piercy, Charle, Verula, Jerik, Burda, Dorota, Montaser, Rugia, Harden, Lesley, Mayangao, Irving, Marriott, Cheryl, Bradley, Paul, Harris, Celia, Cooper, Joshua, Finch, Cheryl, Liderth, Sarah, Quinn, Alison, Waddington, Natalia, Fidler, Katy, Tagliavini, Emma, Donnelly, Kevin, Abel, Lynn, Brett, Michael, Digby, Brian, Gemmell, Lisa, Hornsby, Jame, Macgoey, Patrick, O’Neil, Pauline, Price, Richard, Rodden, Natalie, Rooney, Kevin, Sundaram, Radha, Thomson, Nicola, Flanagan, Rebecca, Hughes, Gareth, Latham, Scott, Mckenna, Emma, Anderson, Jennifer, Hull, Robert, Rhead, Kat, Branney, Debbie, Frankham, Jordan, Pitts, Sally, White, Nigel, Cristiano, Daniele, Dormand, Natalie, Farzad, Zohreh, Gummadi, Mahitha, Liyanage, Kamal, Patel, Brijesh V., Salmi, Sara, Sloane, Geraldine, Varghese, Mathew, Zborowski, Anelise C., Bean, Sarah, Burt, Karen, Spivey, Michael, Eastgate-Jackson, Christine, Filipe, Helder, Martin, Daniel, Maharajh, Amitaa, Garcia, Sara Mingo, De Neef, Mark, Lynch, Ceri, Howe, Gwenllian Sera, Singh, Jayaprakash, Turner, Keri, Ellis, Hannah, Stroud, Natalie, Cherian, Shiney, Cutler, Sean, Heron, Anne Emma, Roynon-Reed, Anna, Williams, Gemma, Richards, Owen, Cheema, Yusuf, Ahmad, Norfaizan, Barker, Joann, Bauchmuller, Kri, Bird, Sarah, Cawthron, Kay, Harrington, Kate, Jackson, Yvonne, Kibutu, Faith, Lenagh, Becky, Masuko, Shamiso, Raithatha, Ajay, Wiles, Matthew, Willson, Jayne, Newell, Helen, Lye, Alison, Nwafor, Lorenza, Jarman, Claire, Rowland-Jones, Sarah, Foote, David, Cole, Joby, Thompson, Roger, Watson, Jame, Hesseldon, Lisa, Macharia, Irene, Chetam, Luke, Smith, Jacqui, Ford, Amber, Anderson, Samantha, Birchall, Kathryn, Housley, Kay, Walker, Sara, Milner, Leanne, Hanratty, Helena, Trower, Helen, Phillips, Patrick, Oxspring, Simon, Donne, Ben, Bevan, Emily, Martin, Jane, Trodd, Dawn, Watson, Geoff, Brown, Caroline Wrey, Bunni, Lara, Jennings, Claire, Latif, Monica, Marshall, Rebecca, Subramanian, Gayathri, Bandla, Nageswar, Gellamucho, Minnie, Davies, Michelle, Thompson, Christopher, Trim, Fiona, Eapen, Beena, Ahmed, Cecilia, Baines, Balvinder, Clamp, Sarah, Colley, Julie, Haq, Risna, Hayes, Anne, Hulme, Jonathan, Hussain, Samia, Joseph, Sibet, Kumar, Rita, Maqsood, Zahira, Purewal, Manjit, Chandler, Ben, Elliott, Kerry, Mallinson, Janine, Turnbull, Alison, Dent, Kathy, Horsley, Elizabeth, Akhtar, Muhmmad Nauman, Pearson, Sandra, Potoczna, Dorota, Spencer, Sue, Blakemore, Hayley, Borislavova, Borislava, Faulkner, Beverley, Gendall, Emma, Goff, Elizabeth, Hayes, Kati, Thomas, Matt, Worner, Ruth, Smith, Kerry, Stephens, Deanna, Delgado, Carlos Castro, Dawson, Deborah, Ding, Lijun, Durrant, Georgia, Ezeobu, Obiageri, Farnell-Ward, Sarah, Harrison, Abiola, Kanu, Rebecca, Leaver, Susannah, Maccacari, Elena, Manna, Soumendu, Saluzzio, Romina Peperman, Queiroz, Joana, Samakomva, Tinashe, Sicat, Christine, Texeira, Joana, Da Gloria, Edna Fernande, Lisboa, Ana, Rawlins, John, Mathew, Jisha, Kinch, Ashley, Hurt, William Jame, Shah, Nirav, Clark, Victoria, Thanasi, Maria, Yun, Nikki, Patel, Kamal, Crickmore, Vikki, Debreceni, Gabor, Wilkins, Joy, Nicol, Liz, Burn, Iona, Hambrook, Geraldine, Manso, Katarina, Penn, Ruth, Shanmugasundaram, Pradeep, Tebbutt, Julie, Thornton, Danielle, Rostron, Anthony, Roy, Alistair, Woods, Lindsey, Cornell, Sarah, Wakinshaw, Fiona, Rogerson, Kimberley, Jarmain, Jordan, Anderson, Peter, Archer, Katie, Austin, Karen, Davis, Caroline, Durie, Alison, Kelsall, Olivia, Thrush, Jessica, Vigurs, Charlie, Wood, Hannah-Louise, Tranter, Helen, Harrison, Alison, Cowley, Nichola, Mcalindon, Michael, Digby, Stephen, Low, Emma, Morgan, Aled, Cother, Naiara, Rankin, Tobia, Clayton, Sarah, Mccurdy, Alex, Allibone, Suzanne, Mary-Genetu, Roman, Patel, Amit, Mac, Ainhi, Murphy, Anthony, Mahjoob, Parisa, Nazari, Roonak, Worsley, Lucy, Fagan, Andrew, Mohamed Ali, Inthakab Ali, Beaumont, Karen, Blunt, Mark, Coton, Zoe, Curgenven, Hollie, Elsaadany, Mohamed, Fernandes, Kay, Ally, Sameena Mohamed, Rangarajan, Harini, Sarathy, Varun, Selvanayagam, Sivarupan, Vedage, Dave, White, Matthew, Fernandez-Roman, Jaime, Hamilton, David O., Johnson, Emily, Johnston, Brian, Martinez, Maria Lopez, Mulla, Suleman, Shaw, David, Waite, Alicia A. C., Waugh, Victoria, Welters, Ingeborg D., Williams, Karen, Bemand, Thoma, Black, Ethel, Rosa, Arnold Dela, Howle, Ryan, Jhanji, Shaman, Baikady, Ravishankar Rao, Tatham, Kate Colette, Thomas, Benjamin, Halkes, Matthew, Mercer, Pauline, Thornton, Lorraine, West, Joe, Baird, Tracy, Ruddy, Jim, Reece-Anthony, Rosie, Birt, Mark, Cowton, Amanda, Kay, Andrea, Kent, Melanie, Potts, Kathryn, Wilkinson, Ami, Naylor, Suzanne, Brown, Ellen, Clark, Michele, Purvis, Sarah, Cole, Jade, Davies, Rhy, Duffin, Donna, Hill, Helen, Player, Ben, Thomas, Emma, Williams, Angharad, Beith, Claire Marie, Black, Karen, Clements, Suzanne, Morrison, Alan, Strachan, Dominic, Taylor, Margaret, Clarkson, Michelle, D’Sylva, Stuart, Norman, Kathryn, Coventry, Tina, Fowler, Susan, Mcgregor, Amanda, Brady, Ailbhe, Chan, Rebekah, Mcivor, Shane, Prady, Helena, Whittle, Helen, Mathew, Bijoy, Clapham, Melanie, Harper, Rosemary, Poultney, Una, Rice, Polly, Mutch, Rachel, Baird, Yolanda, Butler, Aaron, Chadbourn, Indra, Folkes, Linda, Fox, Heather, Gardner, Amy, Gomez, Raquel, Hobden, Gillian, King, Kirsten, Margarson, Michael, Martindale, Tim, Meadows, Emma, Raynard, Dana, Thirlwall, Yvette, Helm, David, Margalef, Jordi, Greer, Sandra, Shuker, Karen, Smuts, Sara, Duffield, Joseph, Smith, Oliver, Mallon, Lewi, Claire, Watkin, Birkinshaw, Isobel, Carter, Joseph, Howard, Kate, Ingham, Joanne, Joy, Rosie, Pearson, Harriet, Roche, Samantha, Scott, Zoe, Knights, Ellen, Price, Alicia, Thomas, Alice, Thorpe, Chri, Abraheem, Azmerelda, Bamford, Peter, Cawley, Kathryn, Dunmore, Charlie, Faulkner, Maria, Girach, Rumanah, Jeffrey, Helen, Jones, Rhianna, London, Emily, Nagra, Imrun, Nasir, Farah, Sainsbury, Hannah, Smedley, Clare, Khade, Reena, Sundar, Ashok, Tsinaslanidis, George, Behan, Teresa, Burnett, Caroline, Hatton, Jonathan, Heeney, Elaine, Mitra, Atideb, Newton, Maria, Pollard, Rachel, Stead, Rachael, Birch, Jenny, Bough, Laura, Goodsell, Josie, Tutton, Rebecca, Williams, Patricia, Williams, Sarah, Winter-Goodwin, Barbara, Auld, Fiona, Donnachie, Joanne, Edmond, Ian, Prentice, Lynn, Runciman, Nikole, Salutous, Dario, Symon, Lesley, Todd, Anne, Turner, Patricia, Short, Abigail, Sweeney, Laura, Murdoch, Euan, Senaratne, Dhaneesha, Burns, Karen, Higham, Andrew, Anderson, Taya, Hawcutt, Dan, O’Malley, Laura, Rad, Laura, Rogers, Naomi, Saunderson, Paula, Allison, Kathryn Sian, Afolabi, Deborah, Whitbread, Jennifer, Jones, Dawn, Dore, Rachael, Lankester, Liana, Nikitas, Nikita, Wells, Colin, Stowe, Bethan, Spencer, Kayleigh, Cathcart, Susanne, Duffy, Katharine, Puxty, Alex, Puxty, Kathryn, Turner, Lynne, Ireland, Jane, Semple, Gary, Barry, Peter, Hilltout, Paula, Evitts, Jayne, Tyler, Amanda, Waldron, Joanne, Irvine, Val, Shelley, Benjamin, Akinkugbe, Olugbenga, Bamford, Alasdair, Beech, Emily, Belfield, Holly, Bell, Michael, Davies, Charlene, Jones, Gareth A. L., Mchugh, Tara, Meghari, Hamza, O’Neill, Lauran, Peters, Mark J., Ray, Samiran, Tomas, Ana Luisa, Gorman, Claire, Gupta, Abhinav, Timlick, Elizabeth, Brady, Rebecca, Bonner, Stephen, Hugill, Keith, Jones, Jessica, Liggett, Steven, Bashyal, Archana, Davidson, Neil, Hutton, Paula, Mckechnie, Stuart, Wilson, Jean, Flint, Neil, Rekha, Patel, Hales, Dawn, Cruz, Carina, Gopal, Shameer, Harris, Nichola, Lake, Victoria, Metherell, Stella, Radford, Elizabeth, Clement, Ian, Patel, Bijal, Gulati, A., Hays, Carole, Webster, K., Hudson, Anne, Webster, Andrea, Stephenson, Elaine, Mccormack, Louise, Slater, Victoria, Nixon, Rachel, Hanson, Helen, Fearby, Maggie, Kelly, Sinead, Bridgett, Victoria, Robinson, Philip, Almaden-Boyle, Christine, Austin, Pauline, Cabrelli, Louise, Cole, Stephen, Casey, Matt, Chapman, Susan, Whyte, Clare, Brayne, Adam, Fisher, Emma, Hunt, Jane, Jackson, Peter, Kaye, Duncan, Love, Nichola, Parkin, Juliet, Tuckey, Victoria, van Koutrik, Lynne, Carter, Sasha, Andrew, Benedict, Findlay, Louise, Adams, Katie, Bruce, Michelle, Connolly, Karen, Duncan, Tracy, T. -Michael, Helen, Lindergard, Gabriella, Hey, Samuel, Fox, Claire, Alfonso, Jordan, Durrans, Laura Jayne, Guerin, Jacinta, Hruska, Martin, Eltayeb, Ayaa, Lamb, Thoma, Hodgkiss, Tracey, Cooper, Lisa, Rothwell, Joanne, Dennis, Catherine, Mcgregor, Alastair, Srikaran, Sinduya, Sukha, Anisha, Davies, Kim, O’Brien, Linda, Omar, Zohra, Perkins, Emma, Lewis, Tracy, Sutherland, Isobel, Brooke, Hollie, Buckley, Sarah, Suarez, Jose Cebrian, Charlesworth, Ruth, Hansson, Karen, Norris, John, Poole, Alice, Rose, Alastair, Sandhu, Rajdeep, Sloan, Brendan, Smithson, Elizabeth, Thirumaran, Muthu, Wagstaff, Veronica, Metcalfe, Alexandra, Camsooksai, Julie, Humphrey, Charlotte, Jenkins, Sarah, Wadams, Beverley, Death, Yasmin, Adams, Colene, Agasou, Anita, Arden, Tracie, Bowes, Amy, Boyle, Pauline, Beekes, Mandy, Button, Heather, Capps, Nigel, Carnahan, Mandy, Carter, Anne, Childs, Danielle, Donaldson, Denise, Hard, Kelly, Hurford, Fran, Hussain, Yasmin, Javaid, Ayesha, Jones, Jame, Jose, Sanal, Leigh, Michael, Martin, Terry, Millward, Helen, Motherwell, Nichola, Rikunenko, Rachel, Stickley, Jo, Summers, Julie, Ting, Louise, Tivenan, Helen, Tonks, Louise, Wilcox, Rebecca, Bokhari, Maria, Lucas, Rachael, Mccormick, Wendy, Ritzema, Jenny, Sanderson, Amanda, Wild, Helen, Baxter, Nicola, Henderson, Steven, Kennedy-Hay, Sophie, Mcparland, Christopher, Rooney, Laura, Sim, Malcolm, Mccreath, Gordan, Brunton, Mark, Caterson, Je, Coles, Holly, Frise, Matthew, Rai, Sabi Gurung, Keating, Liza, Tilney, Emma, Bartley, Shauna, Bhuie, Parminder, Downes, Charlotte, Holding, Kathleen, Riches, Katie, Hilton, Mary, Hayman, Mel, Subramanian, Deepak, Daniel, Priya, Zitter, Letizia, Benyon, Sarah, Marriott, Suzie, Park, Linda, Keenan, Samantha, Gordon, Elizabeth, Quinn, Helen, Baines, Kizzy, Andrew, Gillian, Barclay, Lucy, Callaghan, Marie, Clark, Sarah, Hope, Dave, Marshall, Lucy, Mcculloch, Corrienne, Briton, Kate, Singleton, Jo, Birch, Sophie, Simpson, Kerry, Craig, Jayne, Demetriou, Carrie, Eckbad, Charlotte, Hierons, Sarah, Howie, Lucy, Mitchard, Sarah, Ramos, Lidia, Serrano-Ruiz, Alfredo, White, Katie, Kelly, Fiona, Amin, Vishal, Anastasescu, Elena, Anumakonda, Vikram, Karthik, Komala, Kausar, Rizwana, Reid, Karen, Smith, Jacqueline, Imeson-Wood, Janet, Bellini, Arianna, Bryant, Jade, Mayer, Anton, Pickard, Amy, Roe, Nichola, Sowter, Jason, Howlett, Alex, Criste, Kristine, Cusack, Rebecca, Golder, Kim, Golding, Hannah, Jones, Oliver, Leggett, Samantha, Male, Michelle, Marani, Martyna, Prager, Kirsty, Williams, Toran, Roberts, Belinda, Salmon, Karen, Gondo, Prisca, Hadebe, B., Kayani, Abdul, Masunda, Bridgett, Ahmed, Ashar, Morris, Anna, Jakkula, Sriniva, Long, Kate, Whiteley, Simon, Wilby, Elizabeth, Ogg, Bethan, Moultrie, Sam, Odam, M., Bewley, Jeremy, Garland, Zoe, Grimmer, Lisa, Gumbrill, Bethany, Johnson, Rebekah, Sweet, Katie, Webster, Denise, Efford, Georgia, Bennett, Sara, Goodwin, Emma, Jackson, Matthew, Kent, Alissa, Tibke, Clare, Woodyatt, Wiesia, Zaki, Ahmed, Daniel, Amelia, Finn, Joanne, Saha, Rajnish, Bremmer, Pamela, Allan, J., Geary, T., Houston, Gordon, Meikle, A., O’Brien, P., Bell, Dina, Boyle, Rosalind, Douglas, Katie, Glass, Lynn, Lee, Emma, Lennon, Liz, Rattray, Austin, Charnock, Rob, Mcfarland, Denise, Cosgrove, Denise, Attwood, Ben, Parsons, Penny, Carmody, Siobhain, Oblak, Metod, Popescu, Monica, Thankachen, Mini, Baruah, Rosie, Morris, Sheila, Ferguson, Susie, Shepherd, Amy, Altabaibeh, Abdelhakim, Alvaro, Ana, Gilbert, Kayleigh, Ma, Louise, Mostoles, Loreta, Parmar, Chetan, Simpson, Kathryn, Jetha, Champa, Booker, Lauren, Pratley, Anezka, Cosier, Tracey, Millen, Gemma, Schumacher, Natasha, Weston, Heather, Rand, Jame, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S., Bogaert, Debby, Chand, Meera, Cooke, Graham S., Docherty, Annemarie B., Dunning, Jake, da Silva Filipe, Ana, Fletcher, Tom, Green, Christoper A., Harrison, Ewen M., Hiscox, Julian A., Ijaz, Samreen, Khoo, Saye, Lim, Wei Shen, Mentzer, Alexander J., Merson, Laura, Noursadeghi, Mahdad, Moore, Shona C., Palmarini, Massimo, Paxton, William A., Pollakis, Georgio, Price, Nichola, Rambaut, Andrew, Robertson, David L., Sancho-Shimizu, Vanessa, Scott, Janet T., de Silva, Thushan, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Tedder, Richard S., Thomson, Emma C., Roger Thompson, A. A., Thwaites, Ryan S., Turtle, Lance C. W., Gupta, Rishi K., Palmieri, Carlo, Swann, Olivia V., Zambon, Maria, Dumas, Marc-Emmanuel, Griffin, Julian L., Takats, Zoltan, Chechi, Kanta, Andrikopoulos, Petro, Osagie, Anthonia, Olanipekun, Michael, Liggi, Sonia, Lewis, Matthew R., Correia, Gonçalo dos Santo, Sands, Caroline J., Takis, Panteleimon, Maslen, Lynn, Greenhalf, William, Shaw, Victoria, Mcdonald, Sarah E., Keating, Seán, Ahmed, Katie A., Armstrong, Jane A., Ashworth, Milton, Asiimwe, Innocent G., Bakshi, Siddharth, Barlow, Samantha L., Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin W. A., Clark, Jordan J., Clarke, Emily A., Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chri, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis W. S., Foster, Terry, Garcia-Dorival, Isabel, Gunning, Philip, Hartley, Catherine, Jensen, Rebecca L., Jones, Christopher B., Jones, Trevor R., Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A., Mancini, Maria, Mcdonald, Sarah, Mcevoy, Laurence, Mclauchlan, John, Metelmann, Soeren, Miah, Nahida S., Middleton, Joanna, Mitchell, Joyce, Murphy, Ellen G., Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E., Shears, Rebecca K., Small, Benjamin, Subramaniam, Krishanthi S., Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Flaherty, Lisa, Maziere, Nicole, Cass, Emily, Carracedo, Alejandra Doce, Carlucci, Nicola, Holmes, Anthony, Massey, Hannah, Murphy, Lee, Wrobel, Nicola, Mccafferty, Sarah, Morrice, Kirstie, Maclean, Alan, Armstrong, Ruth, Boz, Ceilia, Brown, Adam, Coutts, Audrey, Cullum, Louise, Day, Nicky, Donnelly, Lorna, Duncan, Esther, Fawkes, Angie, Finernan, Paul, Gilchrist, Tammy, Golightly, Ailsa, Hafezi, Katarzyna, Law, Dawn, Law, Rachel, Law, Sarah, Macgillivray, Louise, Mal, Hanning, Mcmaster, Ellie, Meikle, Jen, Oosthuyzen, Wilna, Paterson, Trevor, Stenhouse, Andrew, Swets, Maaike, Szoor-McElhinney, Helen, Taneski, Filip, Wackett, Tony, Ward, Mairi, Weaver, Jane, Coyle, Judy, Gallagher, Bernadette, Lidstone-Scott, Rebecca, Hamilton, Debbie, Schon, Katherine, Furlong, Anita, Biggs, Heather, Griffiths, Fiona, Andrews, Eleanor, Brickell, Kathy, Smyth, Michelle, Murphy, Lorna, Carson, Gail, Hardwick, Hayley, Donohue, Chloe, Pérez-Tur, Jordi [0000-0002-9111-1712], Martín, Javier [0000-0002-2202-0622], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts General Hospital [Boston], A list of authors and their affiliations appears in the Supplementary Information, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-21-COVR-0039,GenMIS-C,Recherche 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Bocciolone, M., Miozzo, M., Chueca, N., Montano, N., Faverio, P., Preatoni, P., Bonfanti, P., Omodei, P., Castro, P., Ferrer, R., Gualtierotti, R., Gallego-Durán, R., Morilla, R., Haider, S., Marsal, S., Aneli, S., Pelusi, S., Bosari, S., Aliberti, S., Dudman, S., Zheng, T., Pumarola, T., Cejudo, T.G., Monzani, V., Friaza, V., Peter, W., Dopazo, X., May, S., Grimsrud, M.M., Gudbjartsson, D.F., Stefansson, K., Sulem, P., Sveinbjornsson, G., Melsted, P., Norddahl, G., Swerford Moore, K.H., Thorsteinsdottir, U., Holm, H., Alarcón-Riquelme, M.E., Bernardo, D., Martínez-Bueno, M., Rello, S.R., Magi, R., Milani, L., Metspalu, A., Laisk, T., Läll, K., Lepamets, M., Esko, T., Reimann, E., Naaber, P., Laane, E., Pesukova, J., Peterson, P., Kisand, K., Tabri, J., Allos, R., Hensen, K., Starkopf, J., Ringmets, I., Tamm, A., Kallaste, A., Alavere, H., Metsalu, K., Puusepp, M., Kristiansson, K., Koskelainen, S., Perola, M., Donner, K., Kivinen, K., Palotie, A., Bochud, P.Y., Boillat, N., Nussle, S.G., Albrich, W., Pagani, J.L., Zu Bentrup, F.M., Viollet, R.M., Kampouri, E.E., Meuwly, J.Y., D'Acremont, V., Younes, S.E., Albrich, W.C., O'Mahony, L., Kleger, G.R., Kahlert, C.R., Negro, T.R., Carreras, A., Galván-Femenía, I., Farré, X., Cortés, B., Mercader, J.M., Guindo-Martinez, M., Torrents, D., Garcia-Aymerich, J., Castaño-Vinyals, G., Dobaño, C., Gori, M., Mondelli, M.U., Castelli, F., Vaghi, M., Rusconi, S., Montagnani, F., Bargagli, E., Franchi, F., Mazzei, M.A., Cantarini, L., Tacconi, D., Feri, M., Scala, R., Spargi, G., Nencioni, C., Bandini, M., Caldarelli, G.P., Spagnesi, M., Canaccini, A., Ognibene, A., D'Arminio Monforte, A., Girardis, M., Antinori, A., Francisci, D., Schiaroli, E., Scotton, P.G., Panese, S., Scaggiante, R., Monica, M.D., Capasso, M., Fiorentino, G., Castori, M., Aucella, F., Di Biagio, A., Masucci, L., Valente, S., Mandalà, M., Zucchi, P., Giannattasio, F., Coviello, D.A., Mussini, C., Bosio, G., Tavecchia, L., Crotti, L., Rizzi, M., La Rovere, 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Reid, K., Imeson-Wood, J., Bellini, A., Bryant, J., Pickard, A., Roe, N., Sowter, J., Howlett, A., Criste, K., Cusack, R., Golder, K., Golding, H., Jones, O., Leggett, S., Male, M., Marani, M., Prager, K., Williams, T., Roberts, B., Salmon, K., Gondo, P., Kayani, A., Masunda, B., Ahmed, A., Morris, A., Jakkula, S., Long, K., Whiteley, S., Wilby, E., Ogg, B., Moultrie, S., Bewley, J., Garland, Z., Grimmer, L., Gumbrill, B., Sweet, K., Webster, D., Efford, G., Bennett, S., Goodwin, E., Jackson, M., Kent, A., Tibke, C., Woodyatt, W., Zaki, A., Daniel, A., Finn, J., Bremmer, P., Houston, G., O'Brien, P., Bell, D., Boyle, R., Douglas, K., Glass, L., Lee, E., Lennon, L., Rattray, A., Charnock, R., McFarland, D., Cosgrove, D., Attwood, B., Parsons, P., Carmody, S., Oblak, M., Popescu, M., Thankachen, M., Baruah, R., Morris, S., Ferguson, S., Shepherd, A., Altabaibeh, A., Alvaro, A., Gilbert, K., Ma, L., Mostoles, L., Parmar, C., Jetha, C., Booker, L., Pratley, A., Cosier, T., Millen, G., Schumacher, N., Weston, H., Rand, J., Alex, B., Bach, B., Barclay, W.S., Bogaert, D., Chand, M., Cooke, G.S., Docherty, A.B., Dunning, J., da Silva Filipe, A., Fletcher, T., Green, C.A., Harrison, E.M., Hiscox, J.A., Ijaz, S., Khoo, S., Lim, W.S., Mentzer, A.J., Merson, L., Noursadeghi, M., Moore, S.C., Palmarini, M., Paxton, W.A., Pollakis, G., Price, N., Rambaut, A., Robertson, D.L., Sancho-Shimizu, V., Scott, J.T., de Silva, T., Sigfrid, L., Solomon, T., Sriskandan, S., Stuart, D., Tedder, R.S., Thomson, E.C., Roger Thompson, A.A., Thwaites, R.S., Turtle, LCW, Gupta, R.K., Palmieri, C., Swann, O.V., Zambon, M., Dumas, M.E., Griffin, J.L., Takats, Z., Chechi, K., Andrikopoulos, P., Osagie, A., Olanipekun, M., Liggi, S., Lewis, M.R., Correia, GDS, Sands, C.J., Takis, P., Maslen, L., Greenhalf, W., Shaw, V., McDonald, S.E., Ahmed, K.A., Armstrong, J.A., Ashworth, M., Asiimwe, I.G., Bakshi, S., Barlow, S.L., Booth, L., Brennan, B., Bullock, K., Catterall, BWA, Clark, J.J., Clarke, E.A., Cox, H., Dincarslan, O., Dunn, C., Dyer, P., Elliott, A., Evans, A., Finch, L., Fisher, LWS, Foster, T., Garcia-Dorival, I., Gunning, P., Hartley, C., Jensen, R.L., Jones, C.B., Jones, T.R., Khandaker, S., Kiy, R.T., Koukorava, C., Lake, A., Lant, S., Latawiec, D., Lavelle-Langham, L., Lefteri, D., Lett, L., Livoti, L.A., Mancini, M., McDonald, S., McEvoy, L., McLauchlan, J., Metelmann, S., Miah, N.S., Middleton, J., Mitchell, J., Murphy, E.G., Penrice-Randal, R., Pilgrim, J., Prince, T., Reynolds, W., Ridley, P.M., Sales, D., Shaw, V.E., Shears, R.K., Small, B., Subramaniam, K.S., Szemiel, A., Taggart, A., Tanianis-Hughes, J., Trochu, E., van Tonder, L., Wilcock, E., Zhang, J.E., Flaherty, L., Maziere, N., Cass, E., Carracedo, A.D., Carlucci, N., Holmes, A., Massey, H., Murphy, L., Wrobel, N., McCafferty, S., Morrice, K., MacLean, A., Armstrong, R., Boz, C., Coutts, A., Cullum, L., Day, N., Donnelly, L., Duncan, E., Fawkes, A., Finernan, P., Gilchrist, T., Golightly, A., Hafezi, K., Law, D., Law, R., Law, S., Macgillivray, L., Maclean, A., Mal, H., Mcmaster, E., Meikle, J., Oosthuyzen, W., Paterson, T., Stenhouse, A., Swets, M., Szoor-McElhinney, H., Taneski, F., Wackett, T., Ward, M., Weaver, J., Coyle, J., Gallagher, B., Lidstone-Scott, R., Hamilton, D., Schon, K., Furlong, A., Biggs, H., Griffiths, F., Andrews, E., Brickell, K., Smyth, M., Carson, G., Hardwick, H., Donohue, C., Neale, Benjamin M. [0000-0003-1513-6077], Apollo - University of Cambridge Repository, Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Guided Treatment in Optimal Selected Cancer Patients (GUTS), AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, Graduate School, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Niemi, M. E. K., Liao, R. G., Neale, B. M., Pathak, G. A., Andrews, S. J., Schulte, E. C., Karim, M. A., Wendt, F. R., Kim, H. -N., Uddin, M. J., Smith, G. D., Willer, C. J., Buxbaum, J. D., Martin, A. R., Balaconis, M. K., Sankaran, V. G., Brent Richards, J., Eric Kerchberger, V., Kenneth Baillie, J., Dutta, A. K., Uddin, M. M., Perez-Tur, J., Verdugo, R. A., Zarate, R., Medina-Gomez, C., Gomez-Cabrero, D., Cadilla, C. L., Boua, P. R., Fave, M. -J., Lemacon, A., Szentpeteri, J. L., Ahmad, H. F., Kornilov, S. A., Prokic, I., Pearson, N. M., Shelton, J. F., Shastri, A. J., Weldon, C. H., Brouwer, M. C., Vlaar, A. P. J., Joost Wiersinga, W., Algera, A. G., Bogaard, H. J., Bonta, P. I., Grobusch, M. P., Hermans, S. M., Hovius, J. W., de Jong, M. D., Nossent, E. J., Prins, J. M., Schultz, M. J., Stijnis, C. S., Minnaar, R. P., van Uffelen, K. W. J., Wolterman, R. A., Ball, C. A., Mccurdy, S., Hong, E. L., Baltzell, A. H., Goffard, J. -C., Peree, H., Leonard, P., Giot, J. -B., Sauvage, A. -S., Wery, M., Morrison, D. R., Chasse, M., Kaufmann, D. E., Mark Lathrop, G., Davis, L. K., Cox, N. J., Below, J. E., Sealock, J. M., Faucon, A. B., Shuey, M. M., Polikowsky, H. G., Petty, L. E., Shaw, D. M., Chen, H. -H., Ludwig, K. U., Schroder, J., Nothen, M. M., Jensen, B. -E. O., Altmuller, J., Berger, M. M., Gogele, M., Gignoux, C. R., Wicks, S. J., Barnes, K. C., Goldstein, D. B., Reilly, M. P., Gharavi, A. G., O'Byrne, S. M., So, Y. S., Park, S. -K., Kim, H. -L., Kang, C. K., Lee, H. -J., Song, K. -H., Yoon, K. J., Paik, N. -J., Joo, E. -J., Park, W. B., Park, J. S., Park, K. U., Ham, S. Y., Kim, E. S., Kim, H. B., Caceres, M., Lenz, T. L., Julia, A., Holter, J. C., Fernandez, J., Sander, L. E., Banales, J. M., Romero-Gomez, M., Hov, J. R., Karlsen, T. H., Wacker, E. M., Elabd, H., Ruhlemann, M. C., Vadla, M. S., Lenning, O. B., Ozer, O., Kassens, J., Figuera Basso, M. E., Ortiz, A. B., Chercoles, A. G., Holten, A. R., Kildal, A. B., Gluck, A., Nolla, A. C., Dyrhol-Riise, A. M., Spinner, C. D., Hoff, D. A. L., Jimenez, D., Pestana, D., Helbig, E. T., Paraboschi, E. M., Sanchez, F. G., Hernandez, I., Galvan-Femenia, I., Badia, J. R., Muller, K. E., Gaede, K. I., Lippert, L. J., Tellez, L., Gutierrez-Stampa, M. A., Vehreschild, M. J. G. T., Marquie, M., Seilmaier, M. J., Rodriguez-Gandia, M., Ayo, N. I., Martinez, N., Cornely, O. A., Rodrigues, P. M., Espana, P. P., Garcia-Fernandez, A. -E., Fracanzani, A. L., Muniz-Diaz, E., Calderon, E. J., Solligard, E., Medrano, F. J., Muller, F., Afset, J. E., Damas, J. K., Ferrusquia-Acosta, J., Quero, J. H., Guerrero, J. M., Bettini, L. R., Gustad, L. T., Valsecchi, M. G., D'Angio, M., Gallego-Duran, R., Cejudo, T. G., Grimsrud, M. M., Gudbjartsson, D. F., Moore, K. H. S., Alarcon-Riquelme, M. E., Martinez-Bueno, M., Rello, S. R., Lall, K., Bochud, P. -Y., Nussle, S. G., Meyer zu Bentrup, F., Merlet Viollet, R., Guery, B., Hugli, O., Gonseth Nussle, S., Estoppey Younes, S., Rochat Negro, T., Mercader, J. M., Castano-Vinyals, G., Dobano, C., Mondelli, M. U., Mazzei, M. A., Caldarelli, G. P., Monforte, A. D., Scotton, P. G., Monica, M. D., Mandala, M., Coviello, D. A., La Rovere, M. T., Segala, F. V., Mencarelli, M. A., Pinto, A. M., Carriero, M. L., Ann Belli, M., Antoni, M. D., Miraglia, F. G., Parisi, S. G., Squeo, G. M., Botta, G., Hunt, K. A., Trembath, R. C., Martin, H. C., Griffiths, C. J., Curtis, C. J., Huang, Q. Q., Lee, S. H., Macarthur, D., Maclaughlin, B., Smith, A. V., Boughton, A. P., Li, K. W., Lefaive, J., Jannes, C. E., Krieger, J. E., Pereira, A. C., Lima, I. R., Tada, M. T., Mccarthy, M., Lee, J. E., Lee, H. S., Jang, H. Y., Kim, Y. -S., Kwon, K. T., Kim, S. -W., Kim, J. Y., Jang, Y. R., Kim, H., Lee, J. Y., Choe, K. -W., Kang, Y. M., Jee, S. H., Jung, K. J., Schroth, G. P., Desouza, F., Cirulli, E. T., Schiabor Barrett, K. M., Washington, N. L., Lu, J. T., Ramirez, J. M., Grzymski, J. J., Minano, J. I. E., Aguirre, L. A., Lopez-Collazo, E., Lozano-Rodriguez, R., Avendano-Ortiz, J., Arcos, V. T., Montalban-Hernandez, K. M., Quiroga, J. V., Martin-Quiros, A., Nakada, T. -A., Vonk, J. M., Ori, A. P. S., Hernandez Cordero, A. I., Sin, D. D., Bosse, Y., Feng, Y. -C. A., Weiss, S. T., Karlson, E. W., Smoller, J. W., Murphy, S. N., Meigs, J. B., Woolley, A. E., Green, R. C., Perez, E. F., Zollner, S., Sloofman, L. G., Sebra, R. P., Collins, B. L., Sealfon, S. C., Jordan, D. M., Thompson, R. C., Belbin, G. M., Underwood, S. J., Hiester, L. L., Charney, A. W., Beckmann, N. D., Schadt, E. E., Abul-Husn, N. S., Cho, J. H., Kenny, E. E., Loos, R. J. F., Nadkarni, G. N., Huckins, L. M., Ferreira, M. A. R., Abecasis, G. R., Leader, J. B., Cantor, M. N., Justice, A. E., Carey, D. J., Josyula, N. S., Kosmicki, J. A., Horowitz, J. E., Gass, M. C., Hottenga, J. J., de Geus, E. J. C., Nivard, M. G., Ritchie, M. D., Verma, S. S., Vari, M. S., Rahier, J. -F., Bulik, C. M., Landen, M., Ferrero, G. B., Fundin, B., Ismail, S. I., Badji, R. M., Hultstrom, M., Geschwind, D. H., Butte, M. J., Chang, T. S., Caulfield, M. J., Scott, R. H., Odhams, C. A., Karczewski, K. J., Wilson, D. J., Spencer, C. A., Crook, D. W., Wyllie, D. H., O'Connell, A. M., Atkinson, E. G., Walters, R. K., Palmer, D. S., Goldstein, J. I., Kyle Satterstrom, F., Earle, S. G., Lin, S. -K., Rudkin, J. K., Zhao, J. H., Butterworth, A. S., Sun, Y. V., Huffman, J. E., O'Donnell, C. J., Michael Gaziano, J., Ho, Y. -L., Glessner, J. R., Mcguigan, P. J., Moore, L. S. P., Vizcaychipi, M. P., Page, V. J., Aldera, E. L., Cutino-Moguel, M. -T., Durand, I., Hawcutt, D. B., Macmahon, M., Macnaughton, E., Mccullough, K., Mcewen, R., O'Shea, M. K., Pooni, J. S., Wooton, D. G., Bretherick, A. D., Fourman, M. H., Meynert, A. M., Ponting, C. P., Porteous, D. J., Russell, C. D., Wilson, J. F., Drake, T. M., Fairfield, C. J., Knight, S. R., Mclean, K. A., Shaw, C. A., Ho, A. Y. W., Horby, P. W., Mcauley, D., Openshaw, P. J. M., Semple, M. G., Mcgowan, J., Mcguinness, H., Mcneela, F., Bayo, L. -A., Arias, S. S., Conyngham, J. -A., Corral, M. A., de Almeida Martins, L. G., Mclaughlan, D., Mcmorrow, L., Mccormick, J., Mitchell, A. M., Maccallum, N., Hughes, R. A., Jones, T. O., Mcphail, M., Mckenley, I., Sutherland, S. -B., de Gordoa, L. O. -R., Gude, E. T., Macgoey, P., Mckenna, E., Patel, B. V., Zborowski, A. C., Garcia, S. M., Howe, G. S., Heron, A. E., Mills, G. H., Brown, C. W., Akhtar, M. N., Delgado, C. C., Saluzzio, R. P., Da Gloria, E. F., Hurt, W. J., Wood, H. -L., Mcalindon, M., Mccurdy, A., Ali, I. A. M., Ally, S. M., Hamilton, D. O., Lopez Martinez, M., Waite, A. A. C., Welters, I. D., Rosa, A. D., Baikady, R. R., Tatham, K. C., Beith, C. M., Mcgregor, A., Mcivor, S., Allison, K. S., Jones, G. A. L., Mchugh, T., Peters, M. J., Tomas, A. L., Mckechnie, S., Mccormack, L., Michael, H. T., Durrans, L. J., Suarez, J. C., Death, Y., Mccormick, W., Mccreath, G., Rai, S. G., Mcculloch, C., Mcfarland, D., Barclay, W. S., Cooke, G. S., Docherty, A. B., Green, C. A., Harrison, E. M., Hiscox, J. A., Lim, W. S., Mentzer, A. J., Paxton, W. A., Robertson, D. L., Scott, J. T., Tedder, R. S., Thomson, E. C., Thwaites, R. S., Gupta, R. K., Swann, O. V., Dumas, M. -E., Griffin, J. L., Lewis, M. R., dos Santos Correia, G., Sands, C. J., Mcdonald, S. E., Ahmed, K. A., Armstrong, J. A., Asiimwe, I. G., Barlow, S. L., Catterall, B. W. A., Clark, J. J., Clarke, E. A., Fisher, L. W. S., Jensen, R. L., Jones, C. B., Jones, T. R., Kiy, R. T., Livoti, L. A., Mcdonald, S., Mcevoy, L., Mclauchlan, J., Miah, N. S., Moore, S. C., Murphy, E. G., Matthew Ridley, P., Shaw, V. E., Shears, R. K., Subramaniam, K. S., Eunice Zhang, J., Carracedo, A. D., Mccafferty, S., Turtle, L. C. W., Data Science Genetic Epidemiology Lab, Institute for Molecular Medicine Finland, HUS Helsinki and Uusimaa Hospital District, University of Helsinki, Research Programs Unit, Doctoral Programme in Population Health, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, and University of Zurich
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Male ,45/43 ,Autoimmunity ,Autoimmunity/genetics ,Body Mass Index ,COVID-19/genetics ,COVID-19/virology ,Critical Illness ,Female ,Genetic Loci/genetics ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Geographic Mapping ,Hospitalization ,Host-Pathogen Interactions/genetics ,Humans ,Inflammation/complications ,Information Dissemination ,Multifactorial Inheritance ,Racial Groups/genetics ,SARS-CoV-2/pathogenicity ,Smoking ,environmental risk factors ,Q1 ,631/208 ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Genetics, Genome-wide association studies, SARS-CoV-2, Viral infection ,GWAS ,Aetiology ,Lung ,QC ,0303 health sciences ,HERITABILITY ,3. Good health ,covid-19 ,Science & Technology - Other Topics ,Identification (biology) ,Infection ,Human ,631/208/205/2138 ,Settore BIO/11 - Biologia Molecolare ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Clinical Research ,Biodefense ,Genetics ,GENOME-WIDE ASSOCIATION ,Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714 [VDP] ,METAANALYSIS ,1000 Multidisciplinary ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Science & Technology ,Prevention ,Racial Groups ,Pneumonia ,genetic architecture ,Human genetics ,Genetic Loci ,genetic factors ,570 Life sciences ,biology ,030217 neurology & neurosurgery ,Medizin ,Infektionsmedicin ,Genome-wide association studies ,Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Pandemic ,2.1 Biological and endogenous factors ,pandemi ,Multidisciplinary ,article ,Public Health, Global Health, Social Medicine and Epidemiology ,Racial Group ,10124 Institute of Molecular Life Sciences ,Host-Pathogen Interaction ,Multidisciplinary Sciences ,Infectious Diseases ,Host-Pathogen Interactions ,Critical Illne ,COVID-19, GWAS, genetic factors, environmental risk factors, therapy ,Infectious Medicine ,Coronavirus disease 2019 (COVID-19) ,SUSCEPTIBILITY LOCI ,General Science & Technology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Computational biology ,Biology ,Vaccine Related ,692/699/255/2514 ,Environmental risk ,Mendelian randomization ,COVID-19 Host Genetics Initiative ,QH426 ,631/326/596/4130 ,030304 developmental biology ,Inflammation ,therapy ,SARS-CoV-2 ,Human Genome ,COVID-19 ,Genetic architecture ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,Emerging Infectious Diseases ,Good Health and Well Being ,Viral infection ,3111 Biomedicine - Abstract
Niemi, Mari E. K. et al. 39 páginas, figuras y tablas. Contiene material suplementario., 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 diseases3-7. 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.
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- 2021
4. Regulation of Fn14 Receptor and NF-kappa B Underlies Inflammation in Meniere's Disease
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Frejo, L, Requena, T, Okawa, S, Gallego-Martinez, A, Martinez-Bueno, M, Aran, I, Batuecas-Caletrio, A, Benitez-Rosario, J, Espinosa-Sanchez, JM, Fraile-Rodrigo, JJ, Garcia-Arumi, AM, Gonzalez-Aguado, R, Marques, P, Martin-Sanz, E, Perez-Fernandez, N, Perez-Vazquez, P, Perez-Garrigues, H, Santos-Perez, S, Soto-Varela, A, Tapia, MC, Trinidad-Ruiz, G, del Sol, A, Alarcon Riquelme ME, and Lopez-Escamez, JA
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vertigo ,NF-kappa B signaling ,NFKB1 ,TWEAK/Fn14 pathway ,TNFRSF12A ,Meniere's disease ,sensorineural hearing loss - Abstract
Meniere's disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case-control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661-2.627); p = 1.39 x 10(-09)]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 x 10(-11)). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-kappa B. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-kappa B-mediated inflammatory response in MD.
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- 2017
5. Allelic variants in TLR10 gene may influence bilateral affectation and clinical course of Meniere's disease
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Requena T, Gazquez I, Moreno A, Batuecas A, Aran I, Soto-Varela A, Santos-Perez S, Perez N, Perez-Garrigues H, Lopez-Nevot A, Martin E, Sanz R, Perez P, Trinidad G, Alarcon-Riquelme ME, Teggi R, Zagato L, Lopez-Nevot MA, and Lopez-Escamez JA
- Abstract
Toll-like receptors trigger the innate immune response by activating various cell types such us macrophages and lymphocytes. We genotyped SNV of TLR3, TRL7, TLR8 and TLR10 in 863 Spanish and 150 Italian patients with Meniere's disease (MD) and 1,013 controls by using Taqman assays. Real-Time qPCR was used to measure the expression level of TLR10 in peripheral blood leukocytes. The overall dataset showed that the C allele and the CC genotype of rs11096955 in TLR10 gene were more commonly observed in controls than patients (corrected p = 1 × 10(-3), OR = 0.68 [95 % confidence interval, 0.54-0.84] for CC genotype; corrected p = 1.5 × 10(-5), OR = 0.75 [0.66-0.85] for allele C). Moreover, the CC genotype was more frequent in patients with uni- (19 %) than bilateral sensorineural hearing loss (SNHL) (13 %). Logistic regression demonstrated that the time since the onset of MD, Tumarkin crises, hearing stage and rs11096955 were independent factors influencing the risk of bilateral SNHL. In addition, rs11096955 influenced hearing loss progression in patients with bilateral MD. No change in expression of TLR10 was observed according to CC, CA or AA genotypes. Our data suggest that allelic variants of TLR10 gene may influence the susceptibility and time-course of hearing loss of MD in the European population.
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- 2013
6. Defective removal of ribonucleotides from DNA promotes systemic lupus erythematosus
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Günther, C, primary, Kind, B, additional, Reijns, MAM, additional, Berndt, N, additional, Martinez-Bueno, M, additional, Wolf, C, additional, Tüngler, V, additional, Chara, O, additional, Lee, YA, additional, Hübner, N, additional, Bicknell, L, additional, Blum, S, additional, Krug, C, additional, Schmidt, F, additional, Kretschmer, S, additional, Koss, S, additional, Astell, KR, additional, Ramantani, G, additional, Bauerfeind, A, additional, Morris, DL, additional, Graham, DS Cunninghame, additional, Bubeck, D, additional, Leitch, A, additional, Ralston, SH, additional, Blackburn, EA, additional, Gahr, M, additional, Witte, T, additional, Vyse, TJ, additional, Melchers, I, additional, Mangold, E, additional, Nöthen, MM, additional, Aringer, M, additional, Kuhn, A, additional, Lüthke, K, additional, Unger, L, additional, Bley, A, additional, Lorenzi, A, additional, Isaacs, JD, additional, Alexopoulou, D, additional, Conrad, K, additional, Dahl, A, additional, Roers, A, additional, Alarcon-Riquelme, ME, additional, Jackson, AP, additional, and Lee-Kirsch, MA, additional
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- 2015
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7. STAT4 AND BLK BUT NOT BANK1 OR IRF5 ARE ASSOCIATED WITH THE PRIMARY ANTIPHOSPHOLIPID SYNDROME
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Yin, H, Borghi, Mo, Delgado Vega AM, Raschi, E, Broggini, V, Tincani, Angela, Meroni, Pl, and Alarcon Riquelme ME
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- 2009
8. Both risk alleles for FcgRIIA and FcgRIIIA are involved in susceptibility for SLE. A unifying hypothesis
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Magnusson, V, Johanneson, B, Lima, G, Odeberg, J, Alarcon-Segovia, D, Alarcon-Riquelme, ME, Magnusson, V, Johanneson, B, Lima, G, Odeberg, J, Alarcon-Segovia, D, and Alarcon-Riquelme, ME
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- 2004
9. The role of regulatory SNPs in Complex Diseases
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Prokunina, L, Alarcon-Riquelme, ME, Prokunina, L, and Alarcon-Riquelme, ME
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- 2004
10. Salivary Gland Tissue Expression of Fas, FasL, Ro52a, Ro52b, La, CTLA-4, PDCD1 and Orm2 in Primary Sjögren´s Syndrome
- Author
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Bolstad, AI, Eiken, HG, Rosenlund, B, Alarcon-Riquelme, ME, Jonsson, R, Bolstad, AI, Eiken, HG, Rosenlund, B, Alarcon-Riquelme, ME, and Jonsson, R
- Published
- 2003
11. Functional Genomics in the study of Autoimmune Diseases
- Author
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Alarcon-Riquelme, ME and Alarcon-Riquelme, ME
- Published
- 2003
12. A Runx Trio with a Taste for Autoimmunity
- Author
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Alarcon-Riquelme, ME and Alarcon-Riquelme, ME
- Published
- 2003
13. The genetic control of sialadenitis versus arthritis in a NOD.QxB10.Q F2 cross.
- Author
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Johansson, Åsa, Nakken, B, Sundler, M, Lindqvist, AKB, Johannesson, M, Alarcon-Riquelme, ME, Bolstad, AI, Jonsson, R, Skarstein, K, Holmdahl, R, Johansson, Åsa, Nakken, B, Sundler, M, Lindqvist, AKB, Johannesson, M, Alarcon-Riquelme, ME, Bolstad, AI, Jonsson, R, Skarstein, K, and Holmdahl, R
- Abstract
The non-obese diabetic (NOD) mouse spontaneously develops diabetes and sialadenitis. The sialadenitis is characterized by histopathological changes in salivary glands and functional deficit similar to Sjögren's syndrome. In humans, Sjögren's syndrome could be associated with other connective tissue disorders, such as rheumatoid arthritis. In the present study the genetic control of sialadenitis in mice was compared to that of arthritis. We have previously reported a NOD locus, identified in an F2 cross with the H2(q) congenic NOD (NOD.Q) and C57BL/10.Q (B10.Q) strains, that promoted susceptibility to collagen-induced arthritis. The sialadenitis in NOD.Q showed a similar histological phenotype as in NOD, whereas no submandibular gland infiltration was found in B10.Q. The development of sialadenitis was independent of immunization with type II collagen and established arthritis. To identify the genetic control of sialadenitis, a gene segregation experiment was performed on an (NOD.QxB10.Q)F2 cross and genetic mapping of 353 F2 mice revealed one significant locus associated with sialadenitis on chromosome 4, LOD score 4.7. The NOD.Q allele-mediated susceptibility under a recessive inheritance pattern. The genetic control of sialadenitis seemed to be unique in comparison to diabetes and arthritis, as no loci associated with these diseases have been identified at the same location., The first two authors contributed equally to this work.
- Published
- 2002
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14. Family studies in SLE
- Author
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Alarcon-Riquelme, ME and Alarcon-Riquelme, ME
- Published
- 2002
15. The study of the genetics of complex diseases: the example of systemic lupus erythematosus
- Author
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Johansson, Cecilia, Alarcon-Riquelme, ME, Johansson, Cecilia, and Alarcon-Riquelme, ME
- Published
- 2001
16. Cytokine polymorphisms in systemic lupus erythematosus and Sjögren’s syndrome
- Author
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Magnusson, Veronica, Nakken, B, Bolstad, AI, Alarcon-Riquelme, ME, Magnusson, Veronica, Nakken, B, Bolstad, AI, and Alarcon-Riquelme, ME
- Published
- 2001
17. A susceptibility locus for human systemic lupus erythematosus (hSLE1) onchromosome 2q.
- Author
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Lindqvist, AK, Steinsson, K, Johanneson, B, Kristjansdottir, H, Arnasson, A, Grondal, G, Jonasson, I, Magnusson, V, Sturfelt, G, Truedsson, L, Svenungsson, E, Lundberg, I, Terwilliger, JD, Gyllensten, UB, Alarcon-Riquelme, ME, Lindqvist, AK, Steinsson, K, Johanneson, B, Kristjansdottir, H, Arnasson, A, Grondal, G, Jonasson, I, Magnusson, V, Sturfelt, G, Truedsson, L, Svenungsson, E, Lundberg, I, Terwilliger, JD, Gyllensten, UB, and Alarcon-Riquelme, ME
- Published
- 2000
18. Fine mapping of the SLEB2 locus involved in susceptibility to systemiclupus erythematosus.
- Author
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Magnusson, V, Lindqvist, AK, Castillejo-Lopez, C, Kristjansdottir, H, Steinsson, K, Grondal, G, Sturfelt, G, Truedsson, L, Svenungsson, E, Lundberg, I, Gunnarsson, I, Bolstad, AI, Haga, HJ, Jonsson, R, Klareskog, L, Alcocer-Varela, J, Alarcon-Segovia, D, Terwilliger, JD, Gyllensten, UB, Alarcon-Riquelme, ME, Magnusson, V, Lindqvist, AK, Castillejo-Lopez, C, Kristjansdottir, H, Steinsson, K, Grondal, G, Sturfelt, G, Truedsson, L, Svenungsson, E, Lundberg, I, Gunnarsson, I, Bolstad, AI, Haga, HJ, Jonsson, R, Klareskog, L, Alcocer-Varela, J, Alarcon-Segovia, D, Terwilliger, JD, Gyllensten, UB, and Alarcon-Riquelme, ME
- Published
- 2000
19. Genetic analysis of the contribution of IL10 to systemic lupuserythematosus.
- Author
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Alarcon-Riquelme, ME, Lindqvist, AK, Jonasson, I, Johanneson, B, Sandino, S, Alcocer-Varela, J, Granados, J, Kristjansdottir, H, Grondal, G, Svenungsson, E, Lundberg, I, Steinsson, K, Klareskog, L, Sturfelt, G, Truedsson, L, Alarcon-Segovia, D, Gyllensten, UB, Alarcon-Riquelme, ME, Lindqvist, AK, Jonasson, I, Johanneson, B, Sandino, S, Alcocer-Varela, J, Granados, J, Kristjansdottir, H, Grondal, G, Svenungsson, E, Lundberg, I, Steinsson, K, Klareskog, L, Sturfelt, G, Truedsson, L, Alarcon-Segovia, D, and Gyllensten, UB
- Published
- 1999
20. A comparison of genome-scans performed in multicase families with systemiclupus erythematosus from different population groups.
- Author
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Johanneson, B, Steinsson, K, Lindqvist, AK, Kristjansdottir, H, Grondal, G, Sandino, S, Tjernstrom, F, Sturfelt, G, Granados-Arriola, J, Alcocer-Varela, J, Lundberg, I, Jonasson, I, Truedsson, L, Svenungsson, E, Klareskog, L, Alarcon-Segovia, D, Gyllensten, UB, Alarcon-Riquelme, ME, Johanneson, B, Steinsson, K, Lindqvist, AK, Kristjansdottir, H, Grondal, G, Sandino, S, Tjernstrom, F, Sturfelt, G, Granados-Arriola, J, Alcocer-Varela, J, Lundberg, I, Jonasson, I, Truedsson, L, Svenungsson, E, Klareskog, L, Alarcon-Segovia, D, Gyllensten, UB, and Alarcon-Riquelme, ME
- Published
- 1999
21. Association of a haplotype of IRF5 gene with systemic lupus erythematosus in Chinese.
- Author
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Siu HO, Yang W, Lau CS, Chan TM, Wong RW, Wong WH, Lau YL, and Alarcon-Riquelme ME
- Published
- 2008
22. Association of Combined Anti-Ro52/TRIM21 and Anti-Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation.
- Author
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Bettacchioli E, Saraux A, Tison A, Cornec D, Dueymes M, Foulquier N, Hillion S, Roguedas-Contios AM, Benyoussef AA, Alarcon-Riquelme ME, Pers JO, and Devauchelle-Pensec V
- Subjects
- Humans, Female, Middle Aged, Male, Adult, Autoantibodies immunology, Aged, Antibodies, Antinuclear immunology, Sjogren's Syndrome immunology, Ribonucleoproteins immunology, Severity of Illness Index, Interferons, Autoantigens, RNA, Small Cytoplasmic
- Abstract
Objective: The biologic diagnosis of primary Sjögren disease (SjD) mainly relies on anti-Ro60/SSA antibodies, whereas the significance of anti-Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biologic, transcriptomic, and interferon profiles of patients with SjD according to their anti-Ro52/TRIM21 antibody status., Methods: Patients with SjD from the European PRECISESADS (n = 376) and the Brittany Diagnostic Suspicion of primitive Sjögren's Syndrome (DIApSS); (n = 146) cohorts were divided into four groups: double negative (Ro52
- /Ro60- ), isolated anti-Ro52/TRIM21 positive (Ro52+ ), isolated anti-Ro60/SSA positive (Ro60+ ), and double-positive (Ro52+ /Ro60+ ) patients. Clinical information; EULAR Sjögren Syndrome Disease Activity Index, a score representing systemic activity; and biologic markers associated with disease severity were evaluated. Transcriptome data obtained from whole blood by RNA sequencing and type I and II interferon signatures were analyzed for PRECISESADS patients., Results: In the DIApSS cohort, Ro52+ /Ro60+ patients showed significantly more parotidomegaly (33.3% vs 0%-11%) along with higher β2-microglobulin (P = 0.0002), total immunoglobulin (P < 0.0001), and erythrocyte sedimentation rate levels (P = 0.002) as well as rheumatoid factor (RF) positivity (66.2% vs 20.8%-25%) compared to other groups. The PRECISESADS cohort corroborated these observations, with increased arthritis (P = 0.046), inflammation (P = 0.005), hypergammaglobulinemia (P < 0.0001), positive RF (P < 0.0001), leukopenia (P = 0.004), and lymphopenia (P = 0.009) in Ro52+ /Ro60+ patients. Cumulative EULAR Sjögren Syndrome Disease Activity Index results further confirmed these disparities (P = 0.002). Transcriptome analysis linked anti-Ro52/TRIM21 antibody positivity to interferon pathway activation as an underlying cause for these clinical correlations., Conclusion: These results suggest that the combination of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies is associated with a clinical, biologic, and transcriptional profile linked to greater disease severity in SjD through the potentiation of the interferon pathway activation by anti-Ro52/TRIM21 antibodies., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)- Published
- 2024
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23. Type 1 interferons: A target for immune-mediated inflammatory diseases (IMIDs).
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Mathian A, Felten R, Alarcon-Riquelme ME, Psarras A, Mertz P, Chasset F, Vital EM, and Arnaud L
- Subjects
- Humans, Interferons therapeutic use, Immunity, Innate, Immunomodulating Agents, Interferon Type I therapeutic use, Interferon Type I metabolism, Lupus Erythematosus, Systemic drug therapy, Sjogren's Syndrome
- Abstract
The improved understanding of the molecular basis of innate immunity have led to the identification of type I interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis of several Immune-mediated inflammatory diseases (IMIDs) such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myositis and Sjögren's syndrome. Here, we review the main data regarding the opportunity to target type I IFNs for the treatment of IMIDs. Type I IFNs and their downstream pathways can be targeted pharmacologically in several manners. One approach is to use monoclonal antibodies against IFNs or the IFN-receptors (IFNARs, such as with anifrolumab). The downstream signaling pathways of type I IFNs also contain several targets of interest in IMIDs, such as JAK1 and Tyk2. Of these, anifrolumab is licensed and JAK1/Tyk2 inhibitors are in phase III trials in SLE. Targeting IFN-Is for the treatment of SLE is already a reality and in the near future may prove useful in other IMIDs. IFN assays will find a role in routine clinical practice for the care of IMIDs as further validation work is completed and a greater range of targeted therapies becomes available., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
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- View/download PDF
24. Author Correction: Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.
- Author
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Khatri B, Tessneer KL, Rasmussen A, Aghakhanian F, Reksten TR, Adler A, Alevizos I, Anaya JM, Aqrawi LA, Baecklund E, Brun JG, Bucher SM, Eloranta ML, Engelke F, Forsblad-d'Elia H, Glenn SB, Hammenfors D, Imgenberg-Kreuz J, Jensen JL, Johnsen SJA, Jonsson MV, Kvarnström M, Kelly JA, Li H, Mandl T, Martín J, Nocturne G, Norheim KB, Palm Ø, Skarstein K, Stolarczyk AM, Taylor KE, Teruel M, Theander E, Venuturupalli S, Wallace DJ, Grundahl KM, Hefner KS, Radfar L, Lewis DM, Stone DU, Kaufman CE, Brennan MT, Guthridge JM, James JA, Scofield RH, Gaffney PM, Criswell LA, Jonsson R, Eriksson P, Bowman SJ, Omdal R, Rönnblom L, Warner B, Rischmueller M, Witte T, Farris AD, Mariette X, Alarcon-Riquelme ME, Shiboski CH, Wahren-Herlenius M, Ng WF, Sivils KL, Adrianto I, Nordmark G, and Lessard CJ
- Published
- 2023
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25. Author Correction: Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.
- Author
-
Khatri B, Tessneer KL, Rasmussen A, Aghakhanian F, Reksten TR, Adler A, Alevizos I, Anaya JM, Aqrawi LA, Baecklund E, Brun JG, Bucher SM, Eloranta ML, Engelke F, Forsblad-d'Elia H, Glenn SB, Hammenfors D, Imgenberg-Kreuz J, Jensen JL, Johnsen SJA, Jonsson MV, Kvarnström M, Kelly JA, Li H, Mandl T, Martín J, Nocturne G, Norheim KB, Palm Ø, Skarstein K, Stolarczyk AM, Taylor KE, Teruel M, Theander E, Venuturupalli S, Wallace DJ, Grundahl KM, Hefner KS, Radfar L, Lewis DM, Stone DU, Kaufman CE, Brennan MT, Guthridge JM, James JA, Scofield RH, Gaffney PM, Criswell LA, Jonsson R, Eriksson P, Bowman SJ, Omdal R, Rönnblom L, Warner B, Rischmueller M, Witte T, Farris AD, Mariette X, Alarcon-Riquelme ME, Shiboski CH, Wahren-Herlenius M, Ng WF, Sivils KL, Adrianto I, Nordmark G, and Lessard CJ
- Published
- 2022
- Full Text
- View/download PDF
26. Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.
- Author
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Khatri B, Tessneer KL, Rasmussen A, Aghakhanian F, Reksten TR, Adler A, Alevizos I, Anaya JM, Aqrawi LA, Baecklund E, Brun JG, Bucher SM, Eloranta ML, Engelke F, Forsblad-d'Elia H, Glenn SB, Hammenfors D, Imgenberg-Kreuz J, Jensen JL, Johnsen SJA, Jonsson MV, Kvarnström M, Kelly JA, Li H, Mandl T, Martín J, Nocturne G, Norheim KB, Palm Ø, Skarstein K, Stolarczyk AM, Taylor KE, Teruel M, Theander E, Venuturupalli S, Wallace DJ, Grundahl KM, Hefner KS, Radfar L, Lewis DM, Stone DU, Kaufman CE, Brennan MT, Guthridge JM, James JA, Scofield RH, Gaffney PM, Criswell LA, Jonsson R, Eriksson P, Bowman SJ, Omdal R, Rönnblom L, Warner B, Rischmueller M, Witte T, Farris AD, Mariette X, Alarcon-Riquelme ME, Shiboski CH, Wahren-Herlenius M, Ng WF, Sivils KL, Adrianto I, Nordmark G, and Lessard CJ
- Subjects
- Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Sjogren's Syndrome genetics
- Abstract
Sjögren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands., (© 2022. The Author(s).)
- Published
- 2022
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27. Expression Quantitative Trait Locus Analysis in Systemic Sclerosis Identifies New Candidate Genes Associated With Multiple Aspects of Disease Pathology.
- Author
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Kerick M, González-Serna D, Carnero-Montoro E, Teruel M, Acosta-Herrera M, Makowska Z, Buttgereit A, Babaei S, Barturen G, López-Isac E, Lesche R, Beretta L, Alarcon-Riquelme ME, and Martin J
- Subjects
- Adult, Aged, Basic Helix-Loop-Helix Transcription Factors genetics, Female, Genetic Association Studies, Humans, Inhibitor of Differentiation Proteins genetics, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors genetics, Male, Middle Aged, Molecular Targeted Therapy, Nuclear Proteins genetics, Polymorphism, Single Nucleotide, Quantitative Trait Loci, T-Box Domain Proteins genetics, Transcription Factors genetics, Gene Expression Regulation genetics, Scleroderma, Systemic genetics
- Abstract
Objective: To identify the genetic variants that affect gene expression (expression quantitative trait loci [eQTLs]) in systemic sclerosis (SSc) and to investigate their role in the pathogenesis of the disease., Methods: We performed an eQTL analysis using whole-blood sequencing data from 333 SSc patients and 524 controls and integrated them with SSc genome-wide association study (GWAS) data. We integrated our findings from expression modeling, differential expression analysis, and transcription factor binding site enrichment with key clinical features of SSc., Results: We detected 49,123 validated cis-eQTLs from 4,539 SSc-associated single-nucleotide polymorphisms (SNPs) (P
GWAS < 10-5 ). A total of 1,436 genes were within 1 Mb of the 4,539 SSc-associated SNPs. Of those 1,436 genes, 565 were detected as having ≥1 eQTL with an SSc-associated SNP. We developed a strategy to prioritize disease-associated genes based on their expression variance explained by SSc eQTLs (r2 > 0.05). As a result, 233 candidates were identified, 134 (58%) of them associated with hallmarks of SSc and 105 (45%) of them differentially expressed in the blood cells, skin, or lung tissue of SSc patients. Transcription factor binding site analysis revealed enriched motifs of 24 transcription factors (5%) among SSc eQTLs, 5 of which were found to be differentially regulated in the blood cells (ELF1 and MGA), skin (KLF4 and ID4), and lungs (TBX4) of SSc patients. Ten candidate genes (4%) can be targeted by approved medications for immune-mediated diseases, of which only 3 have been tested in clinical trials in patients with SSc., Conclusion: The findings of the present study indicate a new layer to the molecular complexity of SSc, contributing to a better understanding of the pathogenesis of the disease., (© 2021, American College of Rheumatology.)- Published
- 2021
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28. Transcription Factor Activity Inference in Systemic Lupus Erythematosus.
- Author
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Lopez-Dominguez R, Toro-Dominguez D, Martorell-Marugan J, Garcia-Moreno A, Holland CH, Saez-Rodriguez J, Goldman D, Petri MA, Alarcon-Riquelme ME, and Carmona-Saez P
- Abstract
Background: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with diverse clinical manifestations. Although most of the SLE-associated loci are located in regulatory regions, there is a lack of global information about transcription factor (TFs) activities, the mode of regulation of the TFs, or the cell or sample-specific regulatory circuits. The aim of this work is to decipher TFs implicated in SLE., Methods: In order to decipher regulatory mechanisms in SLE, we have inferred TF activities from transcriptomic data for almost all human TFs, defined clusters of SLE patients based on the estimated TF activities and analyzed the differential activity patterns among SLE and healthy samples in two different cohorts. The Transcription Factor activity matrix was used to stratify SLE patients and define sets of TFs with statistically significant differential activity among the disease and control samples., Results: TF activities were able to identify two main subgroups of patients characterized by distinct neutrophil-to-lymphocyte ratio (NLR), with consistent patterns in two independent datasets-one from pediatric patients and other from adults. Furthermore, after contrasting all subgroups of patients and controls, we obtained a significant and robust list of 14 TFs implicated in the dysregulation of SLE by different mechanisms and pathways. Among them, well-known regulators of SLE, such as STAT or IRF, were found, but others suggest new pathways that might have important roles in SLE., Conclusions: These results provide a foundation to comprehend the regulatory mechanism underlying SLE and the established regulatory factors behind SLE heterogeneity that could be potential therapeutic targets.
- Published
- 2021
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29. An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases.
- Author
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Bettacchioli E, Le Gaffric C, Mazeas M, Borghi MO, Frostegard J, Barturen G, Makowska Z, Babei S, Lesche R, Meroni PL, Alarcon-Riquelme ME, and Renaudineau Y
- Abstract
High amount of polyclonal free light chains (FLC) are reported in systemic autoimmune diseases (SAD) and we took advantage of the PRECISESADS study to better characterize them. Serum FLC levels were explored in 1979 patients with SAD (RA, SLE, SjS, Scl, APS, UCTD, MCTD) and 614 healthy controls. Information regarding clinical parameters, disease activity, medications, autoantibodies (Ab) and the interferon α and/or γ scores were recorded. Among SAD patients, 28.4% had raised total FLC (from 12% in RA to 30% in SLE and APS) with a normal kappa/lambda ratio. Total FLC levels were significantly higher in SAD with inflammation, active disease in SLE and SjS, and an impaired pulmonary functional capacity in SSc, while independent from kidney impairment, infection, cancer and treatment. Total FLC concentrations were positively correlated among the 10/17 (58.8%) autoantibodies (Ab) tested with anti-RNA binding protein Ab (SSB, SSA-52/60 kDa, Sm, U1-RNP), anti-dsDNA/nucleosome Ab, rheumatoid factor and negatively correlated with complement fractions C3/C4. Finally, examination of interferon (IFN) expression as a potential driver of FLC overexpression was tested showing an elevated level of total FLC among patients with a high IFNα and IFNγ Kirou's score, a strong IFN modular score, and the detection in the sera of B-cell IFN dependent factors, such as TNF-R1/TNFRSF1A and CXCL10/IP10. In conclusion, an elevated level of FLC, in association with a strong IFN signature, defines a subgroup of SAD patients, including those without renal affectation, characterized by increased disease activity, autoreactivity, and complement reduction., Competing Interests: All authors declare that they have no conflict of interest., (© 2021 The Author(s).)
- Published
- 2021
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30. Antiphospholipid autoantibody detection is important in all patients with systemic autoimmune diseases.
- Author
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Marziale A, Bettacchioli E, Picart G, Nafai S, Galinat H, Meroni PL, Frostegard J, Alarcon-Riquelme ME, and Renaudineau Y
- Subjects
- Abortion, Spontaneous immunology, Adult, Aged, Antibodies, Antiphospholipid immunology, Antibodies, Antiphospholipid metabolism, Autoimmune Diseases blood, Autoimmune Diseases immunology, Complement Activation, Europe epidemiology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Pregnancy, Risk Assessment methods, Thrombosis immunology, Abortion, Spontaneous epidemiology, Antibodies, Antiphospholipid blood, Autoimmune Diseases complications, Thrombosis epidemiology
- Abstract
Antiphospholipid (aPL) autoantibodies are uncommon in systemic autoimmune diseases (SADs). However, the European PRECISESADS study provides the opportunity to better characterize this rare association. The study was composed of 1818 patients with SADs including 453 with systemic lupus erythematosus (SLE), 359 with rheumatoid arthritis (RA), 385 with systemic sclerosis (SSc), 367 with Sjögren's syndrome (SjS), 94 with mixed connective tissue disease (MCTD), and 160 with undifferentiated connective tissue disease (UCTD). Assays used for aPL determination include the lupus anticoagulant (LAC) analysis using the dilute Russell's viper venom time (dRVVT) assay plus anti-cardiolipin (aCL) and anti-aβ2GPI autoantibodies of IgG and IgM isotype. Information regarding clinical and biological characteristics of SAD patients was available. Among SAD patients, the prevalence of aPL differs significantly between two groups: SLE (57.6%) and non-SLE SADs (13.7%, p < 10
-4 ). Next, association between aPL plus thrombosis and miscarriage were observed in both SLE and non-SLE patients. Thrombosis was best predicted in SLE patients by dRVVT (OR = 6.1; IC95:3.5-10.3) and miscarriage by aCL±β2GPI IgG (OR = 2.5; IC95:1.2-5.2); while in non-SLE SADs the best predictors were aCL±β2GPI IgG for thrombosis (OR = 6.6; IC95:2.4-18.4) and aCL±β2GPI IgM for miscarriage (OR = 2.9; IC95:1.2-6.8). In the case of multiple positivity of aPL, the risk for thrombosis and miscarriage was increased. Central nervous system involvement characterized the SLE patients, in contrast to pulmonary and skin fibrosis, valve lesions, hypertension, elevated creatinemia, C4 fraction reduction, platelet reduction and inflammation that characterized the non-SLE SAD patients. Anti-PL determination remains important in SADs patients and should not be restricted to only SLE patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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31. Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches.
- Author
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Chairta P, Nicolaou P, Sokratous K, Galant C, Houssiau F, Oulas A, Spyrou GM, Alarcon-Riquelme ME, Lauwerys BR, and Christodoulou K
- Subjects
- Biomarkers, Biopsy, High-Throughput Screening Assays, Humans, Scleroderma, Systemic pathology, Skin, Proteomics, Scleroderma, Systemic diagnosis
- Abstract
Background: Pathogenesis and aetiology of systemic sclerosis (SSc) are currently unclear, thus rendering disease prognosis, diagnosis and treatment challenging. The aim of this study was to use paired skin biopsy samples from affected and unaffected areas of the same patient, in order to compare the proteomes and identify biomarkers and pathways which are associated with SSc pathogenesis., Methods: Biopsies were obtained from affected and unaffected skin areas of SSc patients. Samples were cryo-pulverised and proteins were extracted and analysed using mass spectrometry (MS) discovery analysis. Differentially expressed proteins were revealed after analysis with the Progenesis QIp software. Pathway analysis was performed using the Enrichr Web server. Using specific criteria, fifteen proteins were selected for further validation with targeted-MS analysis., Results: Proteomic analysis led to the identification and quantification of approximately 2000 non-redundant proteins. Statistical analysis showed that 169 of these proteins were significantly differentially expressed in affected versus unaffected tissues. Pathway analyses showed that these proteins are involved in multiple pathways that are associated with autoimmune diseases (AIDs) and fibrosis. Fifteen of these proteins were further investigated using targeted-MS approaches, and five of them were confirmed to be significantly differentially expressed in SSc affected versus unaffected skin biopsies., Conclusion: Using MS-based proteomics analysis of human skin biopsies from patients with SSc, we identified a number of proteins and pathways that might be involved in SSc progression and pathogenesis. Fifteen of these proteins were further validated, and results suggest that five of them may serve as potential biomarkers for SSc.
- Published
- 2020
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32. Molecular Characterization of Monocyte Subsets Reveals Specific and Distinctive Molecular Signatures Associated With Cardiovascular Disease in Rheumatoid Arthritis.
- Author
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Ruiz-Limon P, Ortega-Castro R, Barbarroja N, Perez-Sanchez C, Jamin C, Patiño-Trives AM, Luque-Tevar M, Ibáñez-Costa A, Perez-Sanchez L, de la Rosa IA, Abalos-Aguilera M, Jimenez-Gomez Y, Calvo-Gutierrez J, Font P, Escudero-Contreras A, Alarcon-Riquelme ME, Collantes-Estevez E, and López-Pedrera C
- Subjects
- Aged, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid etiology, Atherosclerosis etiology, Atherosclerosis metabolism, Atherosclerosis pathology, Biomarkers, Cardiovascular Diseases diagnosis, Cell Line, Computational Biology methods, Female, Gene Expression, Gene Regulatory Networks, Humans, Immunophenotyping, Male, Middle Aged, Risk Assessment, Transcriptome, Arthritis, Rheumatoid complications, Cardiovascular Diseases etiology, Disease Susceptibility, Monocytes immunology, Monocytes metabolism
- Abstract
Objectives: This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed at functionally characterize the monocyte subsets in RA patients, and analyze their involvement in the increased CV risk associated with RA. Methods: The frequencies of monocyte subpopulations in the peripheral blood of 140 RA patients and 145 healthy donors (HDs) included in the PRECISESADS study were determined by flow cytometry. A second cohort of 50 RA patients and 30 HDs was included, of which CD14
+ and CD16+ monocyte subpopulations were isolated using immuno-magnetic selection. Their transcriptomic profiles (mRNA and microRNA), proinflammatory patterns and activated pathways were evaluated and related to clinical features and CV risk. Mechanistic in vitro analyses were further performed. Results: CD14++ CD16+ intermediate monocytes were extended in both cohorts of RA patients. Their increased frequency was associated with the positivity for autoantibodies, disease duration, inflammation, endothelial dysfunction and the presence of atheroma plaques, as well as with the CV risk score. CD14+ and CD16+ monocyte subsets showed distinctive and specific mRNA and microRNA profiles, along with specific intracellular signaling activation, indicating different functionalities. Moreover, that specific molecular profiles were interrelated and associated to atherosclerosis development and increased CV risk in RA patients. In vitro , RA serum promoted differentiation of CD14+ CD16- to CD14++ CD16+ monocytes. Co-culture with RA-isolated monocyte subsets induced differential activation of endothelial cells. Conclusions: Our overall data suggest that the generation of inflammatory monocytes is associated to the autoimmune/inflammatory response that mediates RA. These monocyte subsets, -which display specific and distinctive molecular signatures- might promote endothelial dysfunction and in turn, the progression of atherosclerosis through a finely regulated process driving CVD development in RA.- Published
- 2019
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33. Genetic fine mapping of systemic lupus erythematosus MHC associations in Europeans and African Americans.
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Hanscombe KB, Morris DL, Noble JA, Dilthey AT, Tombleson P, Kaufman KM, Comeau M, Langefeld CD, Alarcon-Riquelme ME, Gaffney PM, Jacob CO, Sivils KL, Tsao BP, Alarcon GS, Brown EE, Croker J, Edberg J, Gilkeson G, James JA, Kamen DL, Kelly JA, McCune J, Merrill JT, Petri M, Ramsey-Goldman R, Reveille JD, Salmon JE, Scofield H, Utset T, Wallace DJ, Weisman MH, Kimberly RP, Harley JB, Lewis CM, Criswell LA, and Vyse TJ
- Subjects
- Black or African American genetics, Female, Genetic Association Studies, Haplotypes, Humans, Male, Models, Genetic, White People genetics, Genetic Predisposition to Disease, Lupus Erythematosus, Systemic genetics, Major Histocompatibility Complex genetics, Polymorphism, Single Nucleotide
- Abstract
Genetic variation within the major histocompatibility complex (MHC) contributes substantial risk for systemic lupus erythematosus, but high gene density, extreme polymorphism and extensive linkage disequilibrium (LD) have made fine mapping challenging. To address the problem, we compared two association techniques in two ancestrally diverse populations, African Americans (AAs) and Europeans (EURs). We observed a greater number of Human Leucocyte Antigen (HLA) alleles in AA consistent with the elevated level of recombination in this population. In EUR we observed 50 different A-C-B-DRB1-DQA-DQB multilocus haplotype sequences per hundred individuals; in the AA sample, these multilocus haplotypes were twice as common compared to Europeans. We also observed a strong narrow class II signal in AA as opposed to the long-range LD observed in EUR that includes class I alleles. We performed a Bayesian model choice of the classical HLA alleles and a frequentist analysis that combined both single nucleotide polymorphisms (SNPs) and classical HLA alleles. Both analyses converged on a similar subset of risk HLA alleles: in EUR HLA- B*08:01 + B*18:01 + (DRB1*15:01 frequentist only) + DQA*01:02 + DQB*02:01 + DRB3*02 and in AA HLA-C*17:01 + B*08:01 + DRB1*15:03 + (DQA*01:02 frequentist only) + DQA*02:01 + DQA*05:01+ DQA*05:05 + DQB*03:19 + DQB*02:02. We observed two additional independent SNP associations in both populations: EUR rs146903072 and rs501480; AA rs389883 and rs114118665. The DR2 serotype was best explained by DRB1*15:03 + DQA*01:02 in AA and by DRB1*15:01 + DQA*01:02 in EUR. The DR3 serotype was best explained by DQA*05:01 in AA and by DQB*02:01 in EUR. Despite some differences in underlying HLA allele risk models in EUR and AA, SNP signals across the extended MHC showed remarkable similarity and significant concordance in direction of effect for risk-associated variants.
- Published
- 2018
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34. Corrigendum to "Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome" [Clin. Immunol. 168 (2016) 25-29].
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Harris VM, Sharma R, Cavett J, Kurien BT, Liu K, Koelsch KA, Rasmussen A, Radfar L, Lewis D, Stone DU, Kaufman CE, Li S, Segal B, Wallace DJ, Weisman MH, Venuturupalli S, Kelly JA, Alarcon-Riquelme ME, Pons-Estel B, Jonsson R, Lu X, Gottenberg JE, Anaya JM, Cunninghame-Graham DS, Huang AJW, Brennan MT, Hughes P, Alevizos I, Miceli-Richard C, Keystone EC, Bykerk VP, Hirschfield G, Xie G, Siminovitch KA, Ng WF, Nordmark G, Bucher SM, Eriksson P, Omdal R, Rhodus NL, Rischmueller M, Rohrer M, Wahren-Herlenius M, Witte T, Mariette X, Lessard CJ, Harley JB, Sivils KL, and Scofield RH
- Published
- 2018
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35. MetaGenyo: a web tool for meta-analysis of genetic association studies.
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Martorell-Marugan J, Toro-Dominguez D, Alarcon-Riquelme ME, and Carmona-Saez P
- Subjects
- Humans, Genetic Association Studies methods, Internet, Metagenomics methods, Software
- Abstract
Background: Genetic association studies (GAS) aims to evaluate the association between genetic variants and phenotypes. In the last few years, the number of this type of study has increased exponentially, but the results are not always reproducible due to experimental designs, low sample sizes and other methodological errors. In this field, meta-analysis techniques are becoming very popular tools to combine results across studies to increase statistical power and to resolve discrepancies in genetic association studies. A meta-analysis summarizes research findings, increases statistical power and enables the identification of genuine associations between genotypes and phenotypes. Meta-analysis techniques are increasingly used in GAS, but it is also increasing the amount of published meta-analysis containing different errors. Although there are several software packages that implement meta-analysis, none of them are specifically designed for genetic association studies and in most cases their use requires advanced programming or scripting expertise., Results: We have developed MetaGenyo, a web tool for meta-analysis in GAS. MetaGenyo implements a complete and comprehensive workflow that can be executed in an easy-to-use environment without programming knowledge. MetaGenyo has been developed to guide users through the main steps of a GAS meta-analysis, covering Hardy-Weinberg test, statistical association for different genetic models, analysis of heterogeneity, testing for publication bias, subgroup analysis and robustness testing of the results., Conclusions: MetaGenyo is a useful tool to conduct comprehensive genetic association meta-analysis. The application is freely available at http://bioinfo.genyo.es/metagenyo/ .
- Published
- 2017
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36. Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere's Disease.
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Frejo L, Requena T, Okawa S, Gallego-Martinez A, Martinez-Bueno M, Aran I, Batuecas-Caletrio A, Benitez-Rosario J, Espinosa-Sanchez JM, Fraile-Rodrigo JJ, García-Arumi AM, González-Aguado R, Marques P, Martin-Sanz E, Perez-Fernandez N, Pérez-Vázquez P, Perez-Garrigues H, Santos-Perez S, Soto-Varela A, Tapia MC, Trinidad-Ruiz G, Del Sol A, Alarcon Riquelme ME, and Lopez-Escamez JA
- Abstract
Meniere's disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case-control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661-2.627); p = 1.39 × 10
-09 ]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans -expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate ( p = 2.42 × 10-11 ). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD.- Published
- 2017
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37. Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome.
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Harris VM, Sharma R, Cavett J, Kurien BT, Liu K, Koelsch KA, Rasmussen A, Radfar L, Lewis D, Stone DU, Kaufman CE, Li S, Segal B, Wallace DJ, Weisman MH, Venuturupalli S, Kelly JA, Alarcon-Riquelme ME, Pons-Estel B, Jonsson R, Lu X, Gottenberg JE, Anaya JM, Cunninghame-Graham DS, Huang AJW, Brennan MT, Hughes P, Alevizos I, Miceli-Richard C, Keystone EC, Bykerk VP, Hirschfield G, Xie G, Siminovitch KA, Ng WF, Nordmark G, Bucher SM, Eriksson P, Omdal R, Rhodus NL, Rischmueller M, Rohrer M, Wahren-Herlenius M, Witte T, Mariette X, Lessard CJ, Harley JB, Sivils KL, and Scofield RH
- Subjects
- Chromosomes, Human, X genetics, Chromosomes, Human, Y genetics, Female, Gene Frequency, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Arthritis, Rheumatoid genetics, Klinefelter Syndrome genetics, Lupus Erythematosus, Systemic genetics, Sjogren's Syndrome genetics
- Abstract
Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p=0.0012 by Fisher's exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fisher's exact test p=NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA., (Published by Elsevier Inc.)
- Published
- 2016
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38. X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome.
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Liu K, Kurien BT, Zimmerman SL, Kaufman KM, Taft DH, Kottyan LC, Lazaro S, Weaver CA, Ice JA, Adler AJ, Chodosh J, Radfar L, Rasmussen A, Stone DU, Lewis DM, Li S, Koelsch KA, Igoe A, Talsania M, Kumar J, Maier-Moore JS, Harris VM, Gopalakrishnan R, Jonsson R, Lessard JA, Lu X, Gottenberg JE, Anaya JM, Cunninghame-Graham DS, Huang AJW, Brennan MT, Hughes P, Illei GG, Miceli-Richard C, Keystone EC, Bykerk VP, Hirschfield G, Xie G, Ng WF, Nordmark G, Eriksson P, Omdal R, Rhodus NL, Rischmueller M, Rohrer M, Segal BM, Vyse TJ, Wahren-Herlenius M, Witte T, Pons-Estel B, Alarcon-Riquelme ME, Guthridge JM, James JA, Lessard CJ, Kelly JA, Thompson SD, Gaffney PM, Montgomery CG, Edberg JC, Kimberly RP, Alarcón GS, Langefeld CL, Gilkeson GS, Kamen DL, Tsao BP, McCune WJ, Salmon JE, Merrill JT, Weisman MH, Wallace DJ, Utset TO, Bottinger EP, Amos CI, Siminovitch KA, Mariette X, Sivils KL, Harley JB, and Scofield RH
- Subjects
- Autoimmune Diseases epidemiology, Case-Control Studies, Chromosomes, Human, X, Female, Gene Dosage, Humans, In Situ Hybridization, Fluorescence, Prevalence, Sarcoidosis epidemiology, Sex Chromosome Aberrations, Sex Distribution, Trisomy, Arthritis, Rheumatoid epidemiology, Liver Cirrhosis, Biliary epidemiology, Lupus Erythematosus, Systemic epidemiology, Sex Chromosome Disorders of Sex Development epidemiology, Sjogren's Syndrome epidemiology
- Abstract
Objective: More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls., Methods: All subjects in this study were female. We identified subjects with 47,XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47,XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction., Results: We found 47,XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47,XXX. There was an excess of 47,XXX among SLE and SS patients., Conclusion: The estimated prevalence of SLE and SS in women with 47,XXX was ∼2.5 and ∼2.9 times higher, respectively, than that in women with 46,XX and ∼25 and ∼41 times higher, respectively, than that in men with 46,XY. No statistically significant increase of 47,XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity., (© 2016, American College of Rheumatology.)
- Published
- 2016
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39. PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6.
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Oparina NY, Delgado-Vega AM, Martinez-Bueno M, Magro-Checa C, Fernández C, Castro RO, Pons-Estel BA, D'Alfonso S, Sebastiani GD, Witte T, Lauwerys BR, Endreffy E, Kovács L, Escudero A, López-Pedrera C, Vasconcelos C, da Silva BM, Frostegård J, Truedsson L, Martin J, Raya E, Ortego-Centeno N, de Los Angeles Aguirre M, de Ramón Garrido E, Palma MJ, Alarcon-Riquelme ME, and Kozyrev SV
- Subjects
- Alternative Splicing, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, 1-3, Genetic Predisposition to Disease, Haplotypes, Humans, Polymorphism, Single Nucleotide, White People genetics, Intracellular Signaling Peptides and Proteins genetics, Linkage Disequilibrium genetics, Lupus Erythematosus, Systemic genetics, Monoacylglycerol Lipases genetics, Nerve Tissue Proteins genetics, Protein Serine-Threonine Kinases genetics, RNA, Messenger genetics
- Abstract
Objectives: To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease., Methods: Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs., Results: Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans., Conclusions: These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2015
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40. Defective removal of ribonucleotides from DNA promotes systemic autoimmunity.
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Günther C, Kind B, Reijns MA, Berndt N, Martinez-Bueno M, Wolf C, Tüngler V, Chara O, Lee YA, Hübner N, Bicknell L, Blum S, Krug C, Schmidt F, Kretschmer S, Koss S, Astell KR, Ramantani G, Bauerfeind A, Morris DL, Cunninghame Graham DS, Bubeck D, Leitch A, Ralston SH, Blackburn EA, Gahr M, Witte T, Vyse TJ, Melchers I, Mangold E, Nöthen MM, Aringer M, Kuhn A, Lüthke K, Unger L, Bley A, Lorenzi A, Isaacs JD, Alexopoulou D, Conrad K, Dahl A, Roers A, Alarcon-Riquelme ME, Jackson AP, and Lee-Kirsch MA
- Subjects
- Cell Proliferation, Cells, Cultured, DNA Mutational Analysis, Gene Expression, Heterozygote, Humans, Interferon Type I genetics, Interferon Type I metabolism, Pyrimidine Dimers genetics, Ribonuclease H genetics, Autoimmunity genetics, DNA Repair, Lupus Erythematosus, Systemic genetics, Pyrimidine Dimers metabolism
- Abstract
Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2-associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity.
- Published
- 2015
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41. Lupus nephritis susceptibility loci in women with systemic lupus erythematosus.
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Chung SA, Brown EE, Williams AH, Ramos PS, Berthier CC, Bhangale T, Alarcon-Riquelme ME, Behrens TW, Criswell LA, Graham DC, Demirci FY, Edberg JC, Gaffney PM, Harley JB, Jacob CO, Kamboh MI, Kelly JA, Manzi S, Moser-Sivils KL, Russell LP, Petri M, Tsao BP, Vyse TJ, Zidovetzki R, Kretzler M, Kimberly RP, Freedman BI, Graham RR, and Langefeld CD
- Subjects
- Adolescent, Adult, Aged, Child, Female, Genome-Wide Association Study, Genotype, HLA-DR2 Antigen genetics, HLA-DR3 Antigen genetics, Humans, Lupus Erythematosus, Systemic epidemiology, Lupus Erythematosus, Systemic physiopathology, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, RNA, Messenger metabolism, White People genetics, Young Adult, Genetic Predisposition to Disease, Lupus Erythematosus, Systemic genetics, Lupus Nephritis genetics
- Abstract
Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5×10(-7)), 16p12 (SLC5A11; P=5.1×10(-7)), 6p22 (ID4; P=7.4×10(-7)), and 8q24.12 (HAS2, SNTB1; P=1.1×10(-6)). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7×10(-5), respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5×10(-6)). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci., (Copyright © 2014 by the American Society of Nephrology.)
- Published
- 2014
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42. Intronic variants in the NFKB1 gene may influence hearing forecast in patients with unilateral sensorineural hearing loss in Meniere's disease.
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Cabrera S, Sanchez E, Requena T, Martinez-Bueno M, Benitez J, Perez N, Trinidad G, Soto-Varela A, Santos-Perez S, Martin-Sanz E, Fraile J, Perez P, Alarcon-Riquelme ME, Batuecas A, Espinosa-Sanchez JM, Aran I, and Lopez-Escamez JA
- Subjects
- Alleles, Disease Progression, Female, Genetic Predisposition to Disease, Haplotypes genetics, Humans, Kaplan-Meier Estimate, Linkage Disequilibrium genetics, Male, Middle Aged, NF-kappa B p50 Subunit genetics, Hearing genetics, Hearing Loss, Sensorineural genetics, Hearing Loss, Sensorineural physiopathology, Introns genetics, Meniere Disease genetics, Meniere Disease physiopathology, Polymorphism, Single Nucleotide genetics
- Abstract
Meniere's disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-κB pathway, such as REL, TNFAIP3, NFKB1 and TNIP1, have been associated with two or more immune-mediated diseases and allelic variations in the TLR10 gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10(-8)), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and p = 0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL.
- Published
- 2014
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43. ABIN1 dysfunction as a genetic basis for lupus nephritis.
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Caster DJ, Korte EA, Nanda SK, McLeish KR, Oliver RK, G'sell RT, Sheehan RM, Freeman DW, Coventry SC, Kelly JA, Guthridge JM, James JA, Sivils KL, Alarcon-Riquelme ME, Scofield RH, Adrianto I, Gaffney PM, Stevens AM, Freedman BI, Langefeld CD, Tsao BP, Pons-Estel BA, Jacob CO, Kamen DL, Gilkeson GS, Brown EE, Alarcon GS, Edberg JC, Kimberly RP, Martin J, Merrill JT, Harley JB, Kaufman KM, Reveille JD, Anaya JM, Criswell LA, Vila LM, Petri M, Ramsey-Goldman R, Bae SC, Boackle SA, Vyse TJ, Niewold TB, Cohen P, and Powell DW
- Subjects
- Animals, DNA-Binding Proteins genetics, Fluorescent Antibody Technique, Humans, Kidney pathology, Kidney physiopathology, Lupus Nephritis etiology, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B physiology, Polymorphism, Single Nucleotide, DNA-Binding Proteins physiology, Lupus Nephritis genetics
- Abstract
The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-κB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-κB and mitogen-activated protein kinase activity.
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- 2013
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44. An ancestry informative marker set for determining continental origin: validation and extension using human genome diversity panels.
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Nassir R, Kosoy R, Tian C, White PA, Butler LM, Silva G, Kittles R, Alarcon-Riquelme ME, Gregersen PK, Belmont JW, De La Vega FM, and Seldin MF
- Subjects
- Asian People genetics, Black People genetics, Cluster Analysis, Genetic Markers, Genotype, Humans, Polymorphism, Single Nucleotide, Principal Component Analysis, White People genetics, Genetics, Population, Genome, Human
- Abstract
Background: Case-control genetic studies of complex human diseases can be confounded by population stratification. This issue can be addressed using panels of ancestry informative markers (AIMs) that can provide substantial population substructure information. Previously, we described a panel of 128 SNP AIMs that were designed as a tool for ascertaining the origins of subjects from Europe, Sub-Saharan Africa, Americas, and East Asia., Results: In this study, genotypes from Human Genome Diversity Panel populations were used to further evaluate a 93 SNP AIM panel, a subset of the 128 AIMS set, for distinguishing continental origins. Using both model-based and relatively model-independent methods, we here confirm the ability of this AIM set to distinguish diverse population groups that were not previously evaluated. This study included multiple population groups from Oceana, South Asia, East Asia, Sub-Saharan Africa, North and South America, and Europe. In addition, the 93 AIM set provides population substructure information that can, for example, distinguish Arab and Ashkenazi from Northern European population groups and Pygmy from other Sub-Saharan African population groups., Conclusion: These data provide additional support for using the 93 AIM set to efficiently identify continental subject groups for genetic studies, to identify study population outliers, and to control for admixture in association studies.
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- 2009
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45. A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus.
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Orrú V, Tsai SJ, Rueda B, Fiorillo E, Stanford SM, Dasgupta J, Hartiala J, Zhao L, Ortego-Centeno N, D'Alfonso S, Arnett FC, Wu H, Gonzalez-Gay MA, Tsao BP, Pons-Estel B, Alarcon-Riquelme ME, He Y, Zhang ZY, Allayee H, Chen XS, Martin J, and Bottini N
- Subjects
- Amino Acid Sequence, Cell Line, Cohort Studies, Humans, Lupus Erythematosus, Systemic enzymology, Models, Molecular, Molecular Sequence Data, Polymorphism, Genetic, Protein Structure, Tertiary, Protein Tyrosine Phosphatase, Non-Receptor Type 22 chemistry, Risk Factors, Sequence Alignment, White People genetics, Lupus Erythematosus, Systemic genetics, Mutation, Missense, Protein Tyrosine Phosphatase, Non-Receptor Type 22 genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 22 metabolism
- Abstract
A gain-of-function R620W polymorphism in the PTPN22 gene, encoding the lymphoid tyrosine phosphatase LYP, has recently emerged as an important risk factor for human autoimmunity. Here we report that another missense substitution (R263Q) within the catalytic domain of LYP leads to reduced phosphatase activity. High-resolution structural analysis revealed the molecular basis for this loss of function. Furthermore, the Q263 variant conferred protection against human systemic lupus erythematosus, reinforcing the proposal that inhibition of LYP activity could be beneficial in human autoimmunity.
- Published
- 2009
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46. Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America.
- Author
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Kosoy R, Nassir R, Tian C, White PA, Butler LM, Silva G, Kittles R, Alarcon-Riquelme ME, Gregersen PK, Belmont JW, De La Vega FM, and Seldin MF
- Subjects
- Americas, Asian People, Black People genetics, Genetic Variation, Genome, Human, Genotype, Geography, Hispanic or Latino genetics, Humans, Mexican Americans, White People genetics, Gene Frequency, Genetics, Population, Population genetics
- Abstract
To provide a resource for assessing continental ancestry in a wide variety of genetic studies, we identified, validated, and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations., (Copyright 2008 Wiley-Liss, Inc.)
- Published
- 2009
- Full Text
- View/download PDF
47. Amerindian ancestry in Argentina is associated with increased risk for systemic lupus erythematosus.
- Author
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Seldin MF, Qi L, Scherbarth HR, Tian C, Ransom M, Silva G, Belmont JW, Gamron S, Allievi A, Palatnik SA, Saurit V, Paira S, Graf C, Guillerón C, Catoggio LJ, Prigione C, Berbotto GA, García MA, Perandones CE, Truedsson L, Abderrahim H, Battagliotti CG, Pons-Estel BA, and Alarcon-Riquelme ME
- Subjects
- Algorithms, Argentina epidemiology, Bayes Theorem, Case-Control Studies, Computational Biology methods, Genetics, Population, Genotype, Geography, Haplotypes, Humans, Logistic Models, Odds Ratio, Polymorphism, Single Nucleotide, Risk Factors, Genetic Predisposition to Disease, Indians, South American genetics, Lupus Erythematosus, Systemic genetics
- Abstract
Previous studies have demonstrated that in admixed populations, West African ancestry is associated with an increased prevalence of systemic lupus erythematosus (SLE). In the current study, the effect of Amerindian ancestry in SLE was examined in an admixed population in Argentina. The Argentine population is predominantly European with approximately 20% Amerindian admixture, and a very small (<2%) contribution from West Africa. The results indicate that Amerindian admixture in this population is associated with a substantial increase in SLE susceptibility risk (Odds Ratio=7.94, P=0.00006). This difference was not due to known demographic factors, including site of collection, age and gender. In addition, there were trends towards significance for Amerindian ancestry influencing renal disease, age of onset and anti-SSA antibodies. These studies suggest that populations with Amerindian admixture, like those with West African admixture, should be considered in future studies to identify additional allelic variants that predispose to SLE.
- Published
- 2008
- Full Text
- View/download PDF
48. The genetics and biology of Irf5-mediated signaling in lupus.
- Author
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Kozyrev SV and Alarcon-Riquelme ME
- Subjects
- Alternative Splicing immunology, Animals, Humans, Interferon Regulatory Factors biosynthesis, Interferon Regulatory Factors immunology, Interferon-alpha blood, Interferon-alpha genetics, Interferon-alpha immunology, Leukocytes immunology, Leukocytes metabolism, Lupus Erythematosus, Systemic blood, Lupus Erythematosus, Systemic immunology, Protein Isoforms biosynthesis, Protein Isoforms genetics, Protein Isoforms immunology, Signal Transduction immunology, Alternative Splicing genetics, Exons immunology, Interferon Regulatory Factors genetics, Lupus Erythematosus, Systemic genetics, Polymorphism, Genetic immunology, Signal Transduction genetics
- Abstract
Recently much attention was attracted to the importance of the type I interferon pathway in the initiation and development of the autoimmune disease systemic lupus erythematosus (SLE). Many SLE patients have increased serum levels of IFN-alpha and display an IFN gene expression "signature" characterized by strong overexpression of IFN-responsive genes in leukocytes and target tissues. Moreover, about 20% of cancer patients treated with IFN-alpha therapy manifest symptoms resembling SLE and some later develop the disease. One of the key genes of the IFN-alpha pathway, IRF5, was found to be strongly associated with SLE. Two functional SNPs lead to alternative splicing and altered steady-state level of IRF5 gene expression. Besides, the gene has a polymorphic inserion/deletion in exon 6, which contributes to the diversity in the isoform pattern of IRF5. Interestingly, recent studies have not found association of IRF5 with the other autoimmune diseases, such as rheumatoid arthritis or psoriasis, suggesting the unique role for IRF5 in the development of lupus. Here, we present the current knowledge on IRF5 genetics and its biological function and discuss the possible ways in which IRF5 contributes to susceptibility to SLE.
- Published
- 2007
- Full Text
- View/download PDF
49. Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort.
- Author
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Thorburn CM, Prokunina-Olsson L, Sterba KA, Lum RF, Seldin MF, Alarcon-Riquelme ME, and Criswell LA
- Subjects
- Adult, Cohort Studies, Female, Haplotypes, Humans, Logistic Models, Lupus Erythematosus, Systemic epidemiology, Lupus Erythematosus, Systemic immunology, Male, Programmed Cell Death 1 Receptor, Antigens, CD genetics, Apoptosis Regulatory Proteins genetics, Genetic Predisposition to Disease, Genetic Variation, Lupus Erythematosus, Systemic ethnology, Lupus Erythematosus, Systemic genetics, Polymorphism, Single Nucleotide
- Abstract
We evaluated the roles of five single-nucleotide polymorphisms (SNPs) within PDCD1, and haplotypes defined by these SNPs, for the development of systemic lupus erythematosus (SLE) and specific sub-phenotypes (nephritis, antiphospholipid antibody positive, arthritis and double-stranded DNA positive) within a multiethnic US cohort of 1036 patients. Family based analyses were performed using 844 simplex families from four ethnic groups (Caucasian, Asian, Hispanic and African American). Subjects were genotyped for five 'tag' SNPs (selected from 15) to provide complete genetic information in all main ethnic groups. We employed transmission disequilibrium testing to assess risk for SLE by allele or haplotype, and multiple logistic regression analysis of SLE cases to examine associations with specific sub-phenotypes. In family based analyses, a haplotype containing the PD1.3A allele was significantly associated with SLE susceptibility among Caucasian families (P=0.01). Among Hispanic families, two novel SNPs were associated with SLE risk (P=0.005 and 0.01). In multivariate logistic regression analyses, five haplotypes were associated with specific sub-phenotypes among the different ethnic groups. These results suggest that PDCD1 genetic variation influences the risk and expression of SLE and that these associations vary according to ethnic background.
- Published
- 2007
- Full Text
- View/download PDF
50. Argentine population genetic structure: large variance in Amerindian contribution.
- Author
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Seldin MF, Tian C, Shigeta R, Scherbarth HR, Silva G, Belmont JW, Kittles R, Gamron S, Allevi A, Palatnik SA, Alvarellos A, Paira S, Caprarulo C, Guillerón C, Catoggio LJ, Prigione C, Berbotto GA, García MA, Perandones CE, Pons-Estel BA, and Alarcon-Riquelme ME
- Subjects
- Asian People genetics, Bayes Theorem, Black People genetics, Gene Frequency, Genetic Markers, Genetic Variation, Genetics, Population, Humans, Mexican Americans genetics, White People genetics, Indians, South American genetics
- Abstract
Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies., ((c) 2006 Wiley-Liss, Inc.)
- Published
- 2007
- Full Text
- View/download PDF
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