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14 results on '"Besse, Céline"'

1. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, Nancy L., Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-González, Pablo, Valero, Sergi, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Sanabria, Ángela, DeStefano, Anita L., Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G., Kunkle, Brian W., Charbonnier, Camille, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A., Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L., Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K., Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L., Vogelgsang, Jonathan, Pineda, Juan A., Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A., Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M. Arfan, Deniz-Naranjo, M. Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A., Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M., Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J., Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H., Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T., Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M., Seidu, Nazib M., Banaj, Nerisa, Armstrong, Nicola J., Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Mecocci, Patrizia, Hoffmann, Per, Holmans, Peter A., Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N., Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A. L., Smith, A. David, Saenz, Aldo, Bizzarro, Alessandra, Lauria, Alessandra, Vacca, Alessandro, Solomon, Alina, Anastasiou, Anna, Richardson, Anna, Boland, Anne, Koivisto, Anne, Daniele, Antonio, Greco, Antonio, Marianthi, Arnaoutoglou, McGuinness, Bernadette, Fin, Bertrand, Ferrari, Camilla, Custodero, Carlo, Ferrarese, Carlo, Ingino, Carlos, Mangone, Carlos, Reyes Toso, Carlos, Martínez, Carmen, Cuesta, Carolina, Muchnik, Carolina, Joachim, Catharine, Ortiz, Cecilia, Besse, Céline, Johansson, Charlotte, Zoia, Chiara Paola, Laske, Christoph, Anastasiou, Costas, Palacio, Dana Lis, Politis, Daniel G., Janowitz, Daniel, Craig, David, Mann, David M., Neary, David, Jürgen, Deckert, Daian, Delphine, Belezhanska, Diyana, Kohler, Eduardo, Castaño, Eduardo M., Koutsouraki, Effrosyni, Chipi, Elena, De Roeck, Ellen, Costantini, Emanuele, Vardy, Emma R. L. C., Piras, Fabrizio, Roveta, Fausto, Piras, Federica, Prestia, Federico Ariel, Assogna, Francesca, Salani, Francesca, Sala, Gessica, Lacidogna, Giordano, Novack, Gisela, Wilcock, Gordon, Thonberg, Håkan, Kölsch, Heike, Weber, Heike, Boecker, Henning, Etchepareborda, Ignacio, Piaceri, Irene, Tuomilehto, Jaakko, Lindström, Jaana, Laczo, Jan, Johnston, Janet, Deleuze, Jean-François, Harris, Jenny, Schott, Jonathan M., Priller, Josef, Bacha, Juan Ignacio, Snowden, Julie, Lisso, Julieta, Mihova, Kalina Yonkova, Traykov, Latchezar, Morelli, Laura, Brusco, Luis Ignacio, Rainer, Malik, Takalo, Mari, Bjerke, Maria, Del Zompo, Maria, Serpente, Maria, Sanchez Abalos, Mariana, Rios, Mario, Peltonen, Markku, Herrman, Martin J., Kohler, Matias, Rojo, Matias, Jones, Matthew, Orsini, Michela, Medel, Nancy, Olivar, Natividad, Fox, Nick C., Salvadori, Nicola, Hooper, Nigel M., Galeano, Pablo, Solis, Patricia, Bastiani, Patrizia, Passmore, Peter, Heun, Reinhard, Antikainen, Riitta, Olaso, Robert, Perneczky, Robert, Germani, Sandra, López-García, Sara, Love, Seth, Mehrabian, Shima, Bagnoli, Silvia, Kochen, Silvia, Andreoni, Simona, Teipel, Stefan, Todd, Stephen, Pickering-Brown, Stuart, Natunen, Teemu, Tegos, Thomas, Laatikainen, Tiina, Strandberg, Timo, Polvikoski, Tuomo M., Matoska, Vaclav, Ciullo, Valentina, Cores, Valeria, Solfrizzi, Vincenzo, Lisetti, Viviana, Sevillano, Zulma, Abdelnour, C., Aguilera, N., Alarcon, E., Alegret, M., Benaque, A., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., de Rojas, I., Diego, S., Espinosa, A., Gailhajenet, A., García-González, P., Gil, S., Guitart, M., González-Pérez, A., Hernández, I., Ibarria, M., Lafuente, A., Macias, J., Maroñas, O., Martín, E., Martínez, M.T., Marquié, M., Mauleón, A., Montrreal, L., Moreno-Grau, S., Moreno, M., Orellana, A., Ortega, G., Pancho, A., Pelejá, E., Pérez-Cordon, A., Pineda, J.A., Preckler, S., Quintela, I., Real, L.M., Rosende-Roca, M., Ruiz, A., Sáez, M.E., Sanabria, A., Serrano-Rios, M., Sotolongo-Grau, O., Tárraga, L., Valero, S., Vargas, L., Adarmes-Gómez, A.D., Alarcón-Martín, E., Alonso, M.D., Álvarez, I., Álvarez, V., Amer-Ferrer, G., Antequera, M., Antúnez, C., Baquero, M., Bernal, M., Blesa, R., Bullido, M.J., Burguera, J.A., Calero, M., Carrillo, F., Carrión-Claro, M., Casajeros, M.J., Clarimón, J., Cruz-Gamero, J.M., de Pancorbo, M.M., del Ser, T., Diez-Fairen, M., Escuela, R., Garrote-Espina, L., Fortea, J., Franco-Macías, E., Frank-García, A., Garcia Madrona, S., Gómez-Garre, P., Hevilla, S., Jesús, S., Labrador Espinosa, M.A., Lage, C., Legaz, A., Lleó, A., Lopez de Munain, A., López-García, S., Macias-García, D., Manzanares, S., Marín, M., Marín-Muñoz, J., Marín, T., Martín Montes, A., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Menéndez-González, M., Mir, P., Molinuevo, J.L., Pastor, P., Pérez Tur, J., Periñán-Tocino, T., Pineda-Sanchez, R., Piñol-Ripoll, G., Rábano, A., Real de Asúa, D., Rodrigo, S., Rodríguez-Rodríguez, E., Royo, J.L., Sanchez del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M.P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, Carol, Bresner, Catherine, Grozeva, Detelina, Bellou, Eftychia, Sommerville, Ewen W., Matthews, F., Leonenko, Ganna, Menzies, Georgina, Windle, Gill, Harwood, Janet, Phillips, Judith, Bennett, K., Luckuck, Lauren, Clare, Linda, Woods, Robert, Saad, Salha, Burholt, Vanessa, Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J., Álvarez, Victoria, Lleó, Alberto, Real, Luis M., Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D., Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M., Mather, Karen A., Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A., Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M., Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J., Ruiz, Agustín, Smith, A David, Saenz, Aldo, Bizzarro, Alessandra, Lauria, Alessandra, Vacca, Alessandro, Solomon, Alina, Anastasiou, Anna, Richardson, Anna, Boland, Anne, Koivisto, Anne, Daniele, Antonio, Greco, Antonio, Marianthi, Arnaoutoglou, McGuinness, Bernadette, Fin, Bertrand, Ferrari, Camilla, Custodero, Carlo, Ferrarese, Carlo, Ingino, Carlos, Mangone, Carlos, Reyes Toso, Carlos, Martínez, Carmen, Cuesta, Carolina, Muchnik, Carolina, Joachim, Catharine, Ortiz, Cecilia, Besse, Céline, Johansson, Charlotte, Zoia, Chiara Paola, Laske, Christoph, Anastasiou, Costas, Palacio, Dana Lis, Politis, Daniel G, Janowitz, Daniel, Craig, David, Mann, David M, Neary, David, Jürgen, Deckert, Daian, Delphine, Belezhanska, Diyana, Kohler, Eduardo, Castaño, Eduardo M, Koutsouraki, Effrosyni, Chipi, Elena, De Roeck, Ellen, Costantini, Emanuele, Vardy, Emma R L C, Piras, Fabrizio, Roveta, Fausto, Piras, Federica, Prestia, Federico Ariel, Assogna, Francesca, Salani, Francesca, Sala, Gessica, Lacidogna, Giordano, Novack, Gisela, Wilcock, Gordon, Thonberg, Håkan, Kölsch, Heike, Weber, Heike, Boecker, Henning, Etchepareborda, Ignacio, Piaceri, Irene, Tuomilehto, Jaakko, Lindström, Jaana, Laczo, Jan, Johnston, Janet, Deleuze, Jean-François, Harris, Jenny, Schott, Jonathan M, Priller, Josef, Bacha, Juan Ignacio, Snowden, Julie, Lisso, Julieta, Mihova, Kalina Yonkova, Traykov, Latchezar, Morelli, Laura, Brusco, Luis Ignacio, Rainer, Malik, Takalo, Mari, Bjerke, Maria, Del Zompo, Maria, Serpente, Maria, Sanchez Abalos, Mariana, Rios, Mario, Peltonen, Markku, Herrman, Martin J, Kohler, Matias, Rojo, Matias, Jones, Matthew, Orsini, Michela, Medel, Nancy, Olivar, Natividad, Fox, Nick C, Salvadori, Nicola, Hooper, Nigel M, Galeano, Pablo, Solis, Patricia, Bastiani, Patrizia, Passmore, Peter, Heun, Reinhard, Antikainen, Riitta, Olaso, Robert, Perneczky, Robert, Germani, Sandra, López-García, Sara, Love, Seth, Mehrabian, Shima, Bagnoli, Silvia, Kochen, Silvia, Andreoni, Simona, Teipel, Stefan, Todd, Stephen, Pickering-Brown, Stuart, Natunen, Teemu, Tegos, Thomas, Laatikainen, Tiina, Strandberg, Timo, Polvikoski, Tuomo M, Matoska, Vaclav, Ciullo, Valentina, Cores, Valeria, Solfrizzi, Vincenzo, Lisetti, Viviana, Sevillano, Zulma, Abdelnour, C., Aguilera, N., Alarcon, E., Alegret, M., Benaque, A., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., Corbatón-Anchuelo, A., de Rojas, I., Diego, S., Espinosa, A., Gailhajenet, A., García-González, P., Gil, S., Guitart, M., González-Pérez, A., Hernández, I., Ibarria, M., Lafuente, A., Macias, J., Maroñas, O., Martín, E., Martínez, M. T., Marquié, M., Mauleón, A., Montrreal, L., Moreno-Grau, S., Moreno, M., Orellana, A., Ortega, G., Pancho, A., Pelejá, E., Pérez-Cordon, A., Pineda, J. A., Preckler, S., Quintela, I., Real, L. M., Rosende-Roca, M., Ruiz, A., Sáez, M. E., Sanabria, A., Serrano-Rios, M., Sotolongo-Grau, O., Tárraga, L., Valero, S., Vargas, L., Adarmes-Gómez, A. D., Alarcón-Martín, E., Alonso, M. D., Álvarez, I., Álvarez, V., Amer-Ferrer, G., Antequera, M., Antúnez, C., Baquero, M., Bernal, M., Blesa, R., Buiza-Rueda, D., Bullido, M. J., Burguera, J. A., Calero, M., Carrillo, F., Carrión-Claro, M., Casajeros, M. J., Clarimón, J., Cruz-Gamero, J. M., de Pancorbo, M. M., Del Ser, T., Diez-Fairen, M., Escuela, R., Garrote-Espina, L., Fortea, J., Franco-Macías, E., Frank-García, A., García-Alberca, J. M., Garcia Madrona, S., Garcia-Ribas, G., Gómez-Garre, P., Hevilla, S., Jesús, S., Labrador Espinosa, M. A., Lage, C., Legaz, A., Lleó, A., Lopez de Munain, A., López-García, S., Macias-García, D., Manzanares, S., Marín, M., Marín-Muñoz, J., Marín, T., Martín Montes, A., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Menéndez-González, M., Mir, P., Molinuevo, J. L., Pastor, P., Pérez Tur, J., Periñán-Tocino, T., Pineda-Sanchez, R., Piñol-Ripoll, G., Rábano, A., Real de Asúa, D., Rodrigo, S., Rodríguez-Rodríguez, E., Royo, J. L., Sanchez Del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M. P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, Carol, Bresner, Catherine, Grozeva, Detelina, Bellou, Eftychia, Sommerville, Ewen W, Matthews, F., Leonenko, Ganna, Menzies, Georgina, Windle, Gill, Harwood, Janet, Phillips, Judith, Bennett, K., Luckuck, Lauren, Clare, Linda, Woods, Robert, Saad, Salha, Burholt, Vanessa, Rongve, Arvid, Brussels Heritage Lab, Clinical sciences, Neuroprotection & Neuromodulation, and Neurology

Subjects
polygenic risk scores, Multidisciplinary, Common variants, Neuroscience(all), neurology, Medizin, General Physics and Astronomy, ddc:500, General Chemistry, Alzheimer's disease, General Biochemistry, Genetics and Molecular Biology, RISK STRATIFICATION
Abstract

The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article. CA extern

Published
2023
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2. Modifying a Game to Study the Impact of an Hostile Environments on Foraging Behavior

Author

Antariksa, Cania, Besse, Céline, Bruijn, Thomas De, Kroes, Brandon, Schaap, Lennard, Vink, Elze De, Schomaker, Judith, Gómez-Maureira, Marcello A., Lopes, Phil, Luz, Filipe, Liapis, Antonios, Engstrom, Henrik, Human Media Interaction, and Digital Society Institute

Subjects
Game design, Serious games, Foraging behavior, Game user research, Human computer interaction (HCI)
Abstract

Video games and game-like experiment tasks are increasingly used to study human behavior. Prior work used such video games to study foraging behavior, including stressors such as hostile entities (i.e. predators). For this study we adapted a 3D video game to assess its potential for studying the impact of hostile environments on human foraging behavior. Two versions of the game were created that varied in terms of hostility, with the hostile condition including predatory non-player characters (NPCs). This pilot aimed to assess the suitability of the modified game for inducing and evaluating stress-related foraging patterns and pinpoint needed modifications for a large-scale study. Participants (n = 18) reported higher levels of stress in the hostile compared to the non-hostile environment. Results of the pilot indicate that modifications are needed to induce more pronounced behavioral effects, as the currently used measures of exploration (e.g., distance traveled; number of gathered items) were not affected by the hostility manipulation. We aim to further develop the game to improve effectiveness of the hostility manipulation and to investigate the effects with more elaborate exploration analyses (e.g., including measures of entropy).

Published
2023
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3. Post-transcriptional regulation of Leishmania fitness gain

Author

PIEL, Laura, SHANMUGHA RAJAN, K., BUSSOTTI, Giovanni, VARET, Hugo, LEGENDRE, Rachel, PROUX, Caroline, DOUCHÉ, Thibaut, GIAI-GIANETTO, Quentin, CHAZE, Thibault, VOJTKOVA, Barbora, GORDON-BAR, Nadav, DONIGER, Tirza, COHEN-CHALAMISH, Smadar, RENGARAJ, Praveenkumar, BESSE, Céline, BOLAND, Anne, SADLOVA, Jovana, DELEUZE, Jean-François, MATONDO, Mariette, UNGER, Ron, VOLF, Petr, MICHAELI, Shulamit, PESCHER, Pascale, SPÄTH, Gerald, Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Paris (UP), Bar-Ilan University [Israël], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biomics (plateforme technologique), Institut Pasteur [Paris], Plateforme de Protéomique / Proteomics platform, Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague] (CU), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Saclay, This work was supported by the Fondation de la Recherche Médicale contract FDT201805005619(LP), the Agence Nationale pour la Recherche Labex ‘Integrative Biology of Emerging InfectiousDiseases’ contract ANR-10-LABX-62-IBEID and Labex ‘French Alliance for Parasitology and HealthCare’ contract ANR-11-LABX-0024 (GFS, LP, PP, GB), the Campus France Franco-Israeli ProgrammeHubert Curien Maimonide 2018 (GFS and SM), the seeding grant from the Institut Pasteur International Department to the LeiSHield Consortium and the EU H2020 project LeiSHield-MATI - REP-778298-1 (GB), the France Génomique National infrastructure, funded as part of the « Investissements d’Avenir » program managed by the Agence Nationale pour la Recherche contract ANR-10-INBS-09 (HV, RL, CP), and the ERD Funds, project CePaViP (CZ.02.1.01/0.0/0.0/ 16_019/0000759) (BV, JS, PV). We thank the CEA-CNRGH for its contribution to the sequencing costs and all the CEA-CNRGH staff who contributed to sample preparation and sequencing for their excellent technical assistance., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Bussotti, Giovanni, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], Leishmania, transcriptomics, posttranscriptional adaptation, [SDV]Life Sciences [q-bio], genomics, [INFO]Computer Science [cs], experimental evolution, [INFO] Computer Science [cs], small nucleolar RNAs, fitness
Abstract

The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver in Leishmania fitness gain in response to environmental change or chemotherapy. How genome instability generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting to in vitro culture. Phenotypic analyses of parasites from early and late stages of culture adaptation revealed an important fitness tradeoff, with selection for accelerated growth (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network driving parasite fitness, with genome instability causing highly reproducible, gene dosage-dependent changes in protein linked to post-transcriptional regulation. These in turn were associated with a gene dosage-independent reduction in flagellar transcripts and a coordinated increase in abundance of coding and non-coding RNAs known to regulate ribosomal biogenesis and protein translation. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification, providing first evidence that Leishmania fitness gain may be controlled by post-transcriptional and epitranscriptomic regulation. Our findings propose a novel model for Leishmania fitness gain, where differential regulation of mRNA stability and the generation of fitness-adapted ribosomes may potentially filter deleterious from beneficial gene dosage effects and provide proteomic robustness to genetically heterogenous, adapting parasite populations. This model challenges the current, genome-centric approach to Leishmania epidemiology and identifies the Leishmania non-coding small RNome as a potential novel source for biomarker discovery.

Published
2021

4. Papuan mitochondrial genomes and the settlement of Sahul

Author

Pedro, Nicole, Brucato, Nicolas, Fernandes, Veronica, André, Mathilde, Saag, Lauri, Pomat, William, Besse, Céline, Boland, Anne, Deleuze, Jean-François, Clarkson, Chris, Sudoyo, Herawati, Metspalu, Mait, Stoneking, Mark, Cox, Murray P., Leavesley, Matthew, Pereira, Luisa, Ricaut, François-Xavier, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Human Genetics, Evolution et Diversité Biologique (EDB), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Lumière - Lyon 2 - UFR de Sciences économiques et de gestion (UL2 UFR SEG), Université Lumière - Lyon 2 (UL2), University of Tartu, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National en Génomique Humaine, Institut de Génomique, CEA, Evry, France, University of Queensland [Brisbane], Eijkman Institute for Molecular Biology [Jakarta], Department of Evolutianory Genetics, Max-Planck-Institut, Statistics and Bioinformatics Group, School of Fundamental Sciences, Massey University, Palmerston North 4442, New Zealand, Archaeology, School of Humanities &Social Sciences, University of Papua New Guinea, Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal, Centre National de la Recherche Scientifique (CNRS), Universidade do Porto = University of Porto, Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Institute of Genomics, University of Tartu, 51010 Tartu, Tartumaa, Estonia

Subjects
Adult, Male, Geological Phenomena, Likelihood Functions, New Guinea, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Population genetics, Human Migration, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Australia, Article, Tasmania, Papua New Guinea, Phylogeography, Mitochondrial genome, Haplotypes, Genome, Mitochondrial, Ethnicity, Humans, Female, Asia, Southeastern, History, Ancient, Phylogeny, ComputingMilieux_MISCELLANEOUS
Abstract

New Guineans represent one of the oldest locally continuous populations outside Africa, harboring among the greatest linguistic and genetic diversity on the planet. Archeological and genetic evidence suggest that their ancestors reached Sahul (present day New Guinea and Australia) by at least 55,000 years ago (kya). However, little is known about this early settlement phase or subsequent dispersal and population structuring over the subsequent period of time. Here we report 379 complete Papuan mitochondrial genomes from across Papua New Guinea, which allow us to reconstruct the phylogenetic and phylogeographic history of northern Sahul. Our results support the arrival of two groups of settlers in Sahul within the same broad time window (50–65 kya), each carrying a different set of maternal lineages and settling Northern and Southern Sahul separately. Strong geographic structure in northern Sahul remains visible today, indicating limited dispersal over time despite major climatic, cultural, and historical changes. However, following a period of isolation lasting nearly 20 ky after initial settlement, environmental changes postdating the Last Glacial Maximum stimulated diversification of mtDNA lineages and greater interactions within and beyond Northern Sahul, to Southern Sahul, Wallacea and beyond. Later, in the Holocene, populations from New Guinea, in contrast to those of Australia, participated in early interactions with incoming Asian populations from Island Southeast Asia and continuing into Oceania.

Published
2020
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5. A novel rare c.-39C>T mutation in the PROS1 5'UTR causing PS deficiency by creating a new upstream translation initiation codone

Author

Labrouche-Colomer, Sylvie, Soukarieh, Omar, Proust, Carole, Mouton, Christine, Huguenin, Yoann, Roux, Maguelonne, Besse, Céline, Boland, Anne, Olaso, Robert, Constans, Joël, Deleuze, Jean-François, Morange, Pierre-Emmanuel, Jaspard-Vinassa, Béatrice, Trégouët, David-Alexandre, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'hématologie, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Recherche en Génomique Humaine, Institut de Génomique, CEA, Evry, France, Centre d'Etude du Polymorphisme Humain (CEPH), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset-Université Paris Cité (UPCité), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by the GENMED Laboratory of Excellence on Medical Genomics [grant number ANR-10-LABX-0013 (to O.S. and M.R.)], the «EPIDEMIOM-VTE» Senior Chair from the Initiative of Excellence of the University of Bordeaux [grant number ANR No.–10–IDEX-03-02 (to D.A.T.)], partially supported by the French Clinical Research Infrastructure Network on Venous Thrombo-Embolism (F-CRIN INNOVTE), and two research programs managed by the National Research Agency (ANR) as part of the French Investment for the Future., ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), ANR-10-LABX-0013,GENMED,Medical Genomics(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset-Université de Paris (UP), Boullé, Christelle, Initiative d'excellence de l'Université de Bordeaux - - IDEX BORDEAUX2010 - ANR-10-IDEX-0003 - IDEX - VALID, and Medical Genomics - - GENMED2010 - ANR-10-LABX-0013 - LABX - VALID

Subjects
Male, Base Sequence, Codon, Initiator, Pedigree, Protein S, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, open reading frame, Protein S deficiency, Young Adult, genomic medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, VINTAGE, Protein Biosynthesis, Humans, Female, Venos Thrombosis, mutation, 5' Untranslated Regions, HeLa Cells
Abstract

International audience; Autosomal dominant inherited Protein S deficiency (PSD) (MIM 612336) is a rare disorder caused by rare mutations, mainly located in the coding sequence of the structural PROS1 gene, and associated with an increased risk of venous thromboembolism. To identify the molecular defect underlying PSD observed in an extended French pedigree with seven PSD affected members in whom no candidate deleterious PROS1 mutation was detected by Sanger sequencing of PROS1 exons and their flanking intronic regions or via an multiplex ligation-dependent probe amplification (MLPA) approach, a whole genome sequencing strategy was adopted. This led to the identification of a never reported C to T substitution at c.-39 from the natural ATG codon of the PROS1 gene that completely segregates with PSD in the whole family. This substitution ACG→ATG creates a new start codon upstream of the main ATG. We experimentally demonstrated in HeLa cells that the variant generates a novel overlapping upstream open reading frame (uORF) and inhibits the translation of the wild-type PS. This work describes the first example of 5'UTR PROS1 mutation causing PSD through the creation of an uORF, a mutation that is not predicted to be deleterious by standard annotation softwares, and emphasizes the need for better exploration of such type of non-coding variations in clinical genomics.

Published
2020
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6. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

Wessel, Jennifer, Chu, Audrey Y, Willems, Sara M, Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A, Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E, An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J, Grarup, Niels, Ehm, Margaret G, Li, Li, Baldridge, Abigail S, Stančáková, Alena, Abrol, Ravinder, Besse, Céline, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F, Garcia, Melissa E, Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A, Layton, Jill C, Li, Man, Hua Zhao, Jing, Meidtner, Karina, Morrison, Alanna C, Nalls, Mike A, Peters, Marjolein J, Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V, Southam, Lorraine, Stoiber, Marcus H, Strawbridge, Rona J., Taylor, Kent D, Varga, Tibor V, Allin, Kristine H, Amin, Najaf, Aponte, Jennifer L, Aung, Tin, Barbieri, Caterina, Bihlmeyer, Nathan A, Boehnke, Michael, Bombieri, Cristina, Bowden, Donald W, Burns, Sean M, Chen, Yuning, Chen, Yii-DerI, Cheng, Ching-Yu, Correa, Adolfo, Czajkowski, Jacek, Dehghan, Abbas, Ehret, Georg B, Eiriksdottir, Gudny, Escher, Stefan A, Farmaki, Aliki-Eleni, Frånberg, Mattias, Gambaro, Giovanni, Giulianini, Franco, Goddard, William A, Goel, Anuj, Gottesman, Omri, Grove, Megan L, Gustafsson, Stefan, Hai, Yang, Hallmans, Göran, Heo, Jiyoung, Hoffmann, Per, Ikram, Mohammad K, Jensen, Richard A, Jørgensen, Marit E, Jørgensen, Torben, Karaleftheri, Maria, Khor, Chiea C, Kirkpatrick, Andrea, Kraja, Aldi T, Kuusisto, Johanna, Lange, Ethan M, Lee, I T, Lee, Wen-Jane, Leong, Aaron, Liao, Jiemin, Liu, Chunyu, Liu, Yongmei, Lindgren, Cecilia M, Linneberg, Allan, Malerba, Giovanni, Mamakou, Vasiliki, Marouli, Eirini, Maruthur, Nisa M, Matchan, Angela, McKean-Cowdin, Roberta, McLeod, Olga, Metcalf, Ginger A, Mohlke, Karen L, Muzny, Donna M, Ntalla, Ioanna, Palmer, Nicholette D, Pasko, Dorota, Peter, Andreas, Rayner, Nigel W, Renström, Frida, Rice, Ken, Sala, Cinzia F, Sennblad, Bengt, Serafetinidis, Ioannis, Smith, Jennifer A, Soranzo, Nicole, Speliotes, Elizabeth K, Stahl, Eli A, Stirrups, Kathleen, Tentolouris, Nikos, Thanopoulou, Anastasia, Torres, Mina, Traglia, Michela, Tsafantakis, Emmanouil, Javad, Sundas, Yanek, Lisa R, Zengini, Eleni, Becker, Diane M, Bis, Joshua C, Brown, James B, Adrienne Cupples, L, Hansen, Torben, Ingelsson, Erik, Karter, Andrew J, Lorenzo, Carlos, Mathias, Rasika A, Norris, Jill M, Peloso, Gina M, Sheu, Wayne H.-H., Toniolo, Daniela, Vaidya, Dhananjay, Varma, Rohit, Wagenknecht, Lynne E, Boeing, Heiner, Bottinger, Erwin P, Dedoussis, George, Deloukas, Panos, Ferrannini, Ele, Franco, Oscar H, Franks, Paul W, Gibbs, Richard A, Gudnason, Vilmundur, Hamsten, Anders, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, Hofman, Albert, Jansson, Jan-Håkan, Langenberg, Claudia, Launer, Lenore J, Levy, Daniel, Oostra, Ben A, O’Donnell, Christopher J, O’Rahilly, Stephen, Padmanabhan, Sandosh, Pankow, James S, Polasek, Ozren, Province, Michael A, Rich, Stephen S, Ridker, Paul M, Rudan, Igor, Schulze, Matthias B, Smith, Blair H, Uitterlinden, André G, Walker, Mark, Watkins, Hugh, Wong, Tien Y, Zeggini, Eleftheria, Sharp, Stephen J, Forouhi, Nita G, Kerrison, Nicola D, Lucarelli, Debora ME, Sims, Matt, Barroso, Inês, McCarthy, Mark I, Arriola, Larraitz, Balkau, Beverley, Barricarte, Aurelio, Gonzalez, Carlos, Grioni, Sara, Kaaks, Rudolf, Key, Timothy J, Navarro, Carmen, Nilsson, Peter M, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, J. Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Sánchez, María–José, Slimani, Nadia, Tjonneland, Anne, Tumino, Rosario, van der A, Daphne L, van der Schouw, Yvonne T, Riboli, Elio, Laakso, Markku, Borecki, Ingrid B, Chasman, Daniel I, Pedersen, Oluf, Psaty, Bruce M, Shyong Tai, E, van Duijn, Cornelia M, Wareham, Nicholas J, Waterworth, Dawn M, Boerwinkle, Eric, Linda Kao, W H, Florez, Jose C, Loos, Ruth J.F., Wilson, James G, Frayling, Timothy M, Siscovick, David S, Dupuis, Josée, Rotter, Jerome I, Meigs, James B, Scott, Robert A, Goodarzi, Mark O, Jennifer Wessel, Audrey Y. Chu, Sara M. Willems, Shuai Wang, Hanieh Yaghootkar, Jennifer A. Brody, Marco Dauriz, Marie France Hivert, Sridharan Raghavan, Leonard Lipovich, Bertha Hidalgo, Keolu Fox, Jennifer E. Huffman, Ping An, Yingchang Lu, Laura J. Rasmussen Torvik, Niels Grarup, Margaret G. Ehm, Li Li, Abigail S. Baldridge, Alena Stančáková, Ravinder Abrol, Céline Besse, Anne Boland, Jette Bork Jensen, Myriam Fornage, Daniel F. Freitag, Melissa E. Garcia, Xiuqing Guo, Kazuo Hara, Aaron Isaacs, Johanna Jakobsdottir, Leslie A. Lange, Jill C. Layton, Man Li, Jing Hua Zhao, Karina Meidtner, Alanna C. Morrison, Mike A. Nalls, Marjolein J. Peter, Maria Sabater Lleal, Claudia Schurmann, Angela Silveira, Albert V. Smith, Lorraine Southam, Marcus H. Stoiber, Rona J. Strawbridge, Kent D. Taylor, Tibor V. Varga, Kristine H. Allin, Najaf Amin, Jennifer L. Aponte, Tin, Aung, Barbieri, CATERINA MARIA, Nathan A. Bihlmeyer, Michael Boehnke, Cristina Bombieri, Donald W. Bowden, Sean M. Burns, Yuning Chen, Yii DerI Chen, Ching Yu Cheng, Adolfo Correa, Jacek Czajkowski, Abbas Dehghan, Georg B. Ehret, Gudny Eiriksdottir, Stefan A. Escher, Aliki Eleni Farmaki, Mattias Frånberg, Giovanni Gambaro, Franco Giulianini, William A. Goddard, Anuj Goel, Omri Gottesman, Megan L. Grove, Stefan Gustafsson, Yang Hai, Göran Hallmans, Jiyoung Heo, Per Hoffmann, Mohammad K. Ikram, Richard A. Jensen, Marit E. Jørgensen, Torben Jørgensen, Maria Karaleftheri, Chiea C. Khor, Andrea Kirkpatrick, Aldi T. Kraja, Johanna Kuusisto, Ethan M. Lange, I. T. Lee, Wen Jane Lee, Aaron Leong, Jiemin Liao, Chunyu Liu, Yongmei Liu, Cecilia M. Lindgren, Allan Linneberg, Giovanni Malerba, Vasiliki Mamakou, Eirini Marouli, Nisa M. Maruthur, Angela Matchan, Roberta McKean Cowdin, Olga McLeod, Ginger A. Metcalf, Karen L. Mohlke, Donna M. Muzny, Ioanna Ntalla, Nicholette D. Palmer, Dorota Pasko, Andreas Peter, Nigel W. Rayner, Frida Renström, Ken Rice, Cinzia F. Sala, Bengt Sennblad, Ioannis Serafetinidis, Jennifer A. Smith, Nicole Soranzo, Elizabeth K. Speliote, Eli A. Stahl, Kathleen Stirrup, Nikos Tentolouris, Anastasia Thanopoulou, Mina Torres, Michela Traglia, Emmanouil Tsafantakis, Sundas Javad, Lisa R. Yanek, Eleni Zengini, Diane M. Becker, Joshua C. Bi, James B. Brown, L. Adrienne Cupple, Torben Hansen, Erik Ingelsson, Andrew J. Karter, Carlos Lorenzo, Rasika A. Mathias, Jill M. Norri, Gina M. Peloso, Wayne H. H. Sheu, Daniela Toniolo, Dhananjay Vaidya, Rohit Varma, Lynne E. Wagenknecht, Heiner Boeing, Erwin P. Bottinger, George Dedoussis, Panos Delouka, Ele Ferrannini, Oscar H. Franco, Paul W. Franks, Richard A. Gibb, Vilmundur Gudnason, Anders Hamsten, Tamara B. Harris, Andrew T. Hattersley, Caroline Hayward, Albert Hofman, Jan Håkan Jansson, Claudia Langenberg, Lenore J. Launer, Daniel Levy, Ben A. Oostra, Christopher J. O’Donnell, Stephen O’Rahilly, Sandosh Padmanabhan, James S. Pankow, Ozren Polasek, Michael A. Province, Stephen S. Rich, Paul M. Ridker, Igor Rudan, Matthias B. Schulze, Blair H. Smith, André G. Uitterlinden, Mark Walker, Hugh Watkins, Tien Y. Wong, Eleftheria Zeggini, The EPIC InterAct Consortium, Markku Laakso, Ingrid B. Borecki, Daniel I. Chasman, Oluf Pedersen, Bruce M. Psaty, E. Shyong Tai, Cornelia M. van Duijn, Nicholas J. Wareham, Dawn M. Waterworth, Eric Boerwinkle, W. H. Linda Kao, Jose C. Florez, Ruth J. F. Loos, James G. Wilson, Timothy M. Frayling, David S. Siscovick, Josée Dupuis, Jerome I. Rotter, James B. Meigs, Robert A. Scott, Mark O., Goodarzi, Wessel, Jennifer, Chu, Audrey Y, Willems, Sara M, Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A, Dauriz, Marco, Hivert, Marie France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E, An, Ping, Lu, Yingchang, Rasmussen Torvik, Laura J, Grarup, Niel, Ehm, Margaret G, Li, Li, Baldridge, Abigail S, Stančáková, Alena, Abrol, Ravinder, Besse, Céline, Boland, Anne, Bork Jensen, Jette, Fornage, Myriam, Freitag, Daniel F, Garcia, Melissa E, Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A, Layton, Jill C, Li, Man, Hua Zhao, Jing, Meidtner, Karina, Morrison, Alanna C, Nalls, Mike A, Peters, Marjolein J, Sabater Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V, Southam, Lorraine, Stoiber, Marcus H, Strawbridge, Rona J, Taylor, Kent D, Varga, Tibor V, Allin, Kristine H, Amin, Najaf, Aponte, Jennifer L, Aung, Tin, Barbieri, Caterina, Bihlmeyer, Nathan A, Boehnke, Michael, Bombieri, Cristina, Bowden, Donald W, Burns, Sean M, Chen, Yuning, Chen, Yii DerI, Cheng, Ching Yu, Correa, Adolfo, Czajkowski, Jacek, Dehghan, Abba, Ehret, Georg B, Eiriksdottir, Gudny, Escher, Stefan A, Farmaki, Aliki Eleni, Frånberg, Mattia, Gambaro, Giovanni, Giulianini, Franco, Goddard, William A, Goel, Anuj, Gottesman, Omri, Grove, Megan L, Gustafsson, Stefan, Hai, Yang, Hallmans, Göran, Heo, Jiyoung, Hoffmann, Per, Ikram, Mohammad K, Jensen, Richard A, Jørgensen, Marit E, Jørgensen, Torben, Karaleftheri, Maria, Khor, Chiea C, Kirkpatrick, Andrea, Kraja, Aldi T, Kuusisto, Johanna, Lange, Ethan M, Lee, I. T, Lee, Wen Jane, Leong, Aaron, Liao, Jiemin, Liu, Chunyu, Liu, Yongmei, Lindgren, Cecilia M, Linneberg, Allan, Malerba, Giovanni, Mamakou, Vasiliki, Marouli, Eirini, Maruthur, Nisa M, Matchan, Angela, McKean Cowdin, Roberta, Mcleod, Olga, Metcalf, Ginger A, Mohlke, Karen L, Muzny, Donna M, Ntalla, Ioanna, Palmer, Nicholette D, Pasko, Dorota, Peter, Andrea, Rayner, Nigel W, Renström, Frida, Rice, Ken, Sala, Cinzia F, Sennblad, Bengt, Serafetinidis, Ioanni, Smith, Jennifer A, Soranzo, Nicole, Speliotes, Elizabeth K, Stahl, Eli A, Stirrups, Kathleen, Tentolouris, Niko, Thanopoulou, Anastasia, Torres, Mina, Traglia, Michela, Tsafantakis, Emmanouil, Javad, Sunda, Yanek, Lisa R, Zengini, Eleni, Becker, Diane M, Bis, Joshua C, Brown, James B, Cupples, L. Adrienne, Hansen, Torben, Ingelsson, Erik, Karter, Andrew J, Lorenzo, Carlo, Mathias, Rasika A, Norris, Jill M, Peloso, Gina M, Sheu, Wayne H. H, Toniolo, Daniela, Vaidya, Dhananjay, Varma, Rohit, Wagenknecht, Lynne E, Boeing, Heiner, Bottinger, Erwin P, Dedoussis, George, Deloukas, Pano, Ferrannini, Ele, Franco, Oscar H, Franks, Paul W, Gibbs, Richard A, Gudnason, Vilmundur, Hamsten, Ander, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, Hofman, Albert, Jansson, Jan Håkan, Langenberg, Claudia, Launer, Lenore J, Levy, Daniel, Oostra, Ben A, O'Donnell, Christopher J, O'Rahilly, Stephen, Padmanabhan, Sandosh, Pankow, James S, Polasek, Ozren, Province, Michael A, Rich, Stephen S, Ridker, Paul M, Rudan, Igor, Schulze, Matthias B, Smith, Blair H, Uitterlinden, André G, Walker, Mark, Watkins, Hugh, Wong, Tien Y, Zeggini, Eleftheria, Laakso, Markku, Borecki, Ingrid B, Chasman, Daniel I, Pedersen, Oluf, Psaty, Bruce M, Tai, E. Shyong, van Duijn, Cornelia M, Wareham, Nicholas J, Waterworth, Dawn M, Boerwinkle, Eric, Kao, W. H. Linda, Florez, Jose C, Loos, Ruth J. F, Wilson, James G, Frayling, Timothy M, Siscovick, David S, Dupuis, Josée, Rotter, Jerome I, Meigs, James B, Scott, Robert A, Goodarzi, Mark O., Panico, Salvatore, Soranzo, Nicole [0000-0003-1095-3852], Johnson, Kathleen [0000-0002-6823-3252], Langenberg, Claudia [0000-0002-5017-7344], O'Rahilly, Stephen [0000-0003-2199-4449], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Epidemiology, Surgery, Internal Medicine, Radiology & Nuclear Medicine, Clinical Genetics, Obstetrics & Gynecology, and Cell biology

Subjects
Blood Glucose, diabetes, exome chip, SEQUENCING DATA, European Continental Ancestry Group, Black People, Genetic Association Studie, Endocrinology and Diabetes, TRIGLYCERIDE LEVELS, Polymorphism, Single Nucleotide, Article, White People, Glucagon-Like Peptide-1 Receptor, Cohort Studies, SDG 3 - Good Health and Well-being, Mutation Rate, GLYCEMIC TRAITS, Humans, Settore MED/14 - NEFROLOGIA, Insulin, Exome, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Genetic Association Studies, African Continental Ancestry Group, Oligonucleotide Array Sequence Analysis, PLASMA-GLUCOSE, INSULIN-RESISTANCE, epidemiology/genetics, Science & Technology, GLUCAGON-LIKE PEPTIDE-1, Diabetes, Genetic Variation, GERMLINE MUTATIONS, Fasting, epidemiology/genetics, Cohort Studies, Exome, diabetes, Multidisciplinary Sciences, RECEPTOR GENE, Diabetes Mellitus, Type 2, Genetic Loci, Endokrinologi och diabetes, CODING VARIATION, Glucose-6-Phosphatase, Science & Technology - Other Topics, exome chip, Human
Abstract

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=−0.09±0.01 mmol l−1, P=3.4 × 10−12), T2D risk (OR[95%CI]=0.86[0.76–0.96], P=0.010), early insulin secretion (β=−0.07±0.035 pmolinsulin mmolglucose−1, P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l−1, P=4.3 × 10−4). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10−6) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l−1, P=1.3 × 10−8). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility., Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1R significantly associated with these traits.

Published
2015

7. Additional file 2: of Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes

Author

Curtit, Elsa, Pivot, Xavier, Henriques, Julie, Paget-Bailly, Sophie, Fumoleau, Pierre, Rios, Maria, Bonnefoi, Hervé, Bachelot, Thomas, Soulié, Patrick, Jouannaud, Christelle, Bourgeois, Hugues, Petit, Thierry, Tennevet, Isabelle, Assouline, David, Marie-Christine Mathieu, Jean-Philippe Jacquin, Lavau-Denes, Sandrine, Darut-Jouve, Ariane, Jean-Marc Ferrero, Tarpin, Carole, Lévy, Christelle, Delecroix, Valérie, Trillet-Lenoir, Véronique, Cojocarasu, Oana, Meunier, Jérôme, Jean-Yves Pierga, Kerbrat, Pierre, Faure-Mercier, Céline, Blanché, Hélène, Sahbatou, Mourad, Boland, Anne, Bacq, Delphine, Besse, Céline, Thomas, Gilles, Jean-François Deleuze, Pauporté, Iris, Romieu, Gilles, and Cox, David

Abstract

Supplementary methods. supplementary data on subject recruiting, blood collection, DNA extraction, genotyping and imputation. (DOCX 26 kb)

Published
2017
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8. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

Wessel, Jennifer, Chu, Audrey Y, Willems, Sara M, Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A, Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E, An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J, Grarup, Niels, Ehm, Margaret G, Li, Li, Baldridge, Abigail S, Stančáková, Alena, Abrol, Ravinder, Besse, Céline, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F, Garcia, Melissa E, Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A, Layton, Jill C, Li, Man, Hua Zhao, Jing, Meidtner, Karina, Morrison, Alanna C, Nalls, Mike A, Peters, Marjolein J, Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V, Southam, Lorraine, Stoiber, Marcus H, Strawbridge, Rona J, Taylor, Kent D, Varga, Tibor V, Allin, Kristine H, Amin, Najaf, Aponte, Jennifer L, Aung, Tin, Barbieri, Caterina, Bihlmeyer, Nathan A, Boehnke, Michael, Bombieri, Cristina, Bowden, Donald W, Burns, Sean M, Chen, Yuning, Chen, Yii-DerI, Cheng, Ching-Yu, Correa, Adolfo, Czajkowski, Jacek, Dehghan, Abbas, Ehret, Georg B, Eiriksdottir, Gudny, Escher, Stefan A, Farmaki, Aliki-Eleni, Frånberg, Mattias, Gambaro, Giovanni, Giulianini, Franco, Goddard, William A, Goel, Anuj, Gottesman, Omri, Grove, Megan L, Gustafsson, Stefan, Hai, Yang, Hallmans, Göran, Heo, Jiyoung, Hoffmann, Per, Ikram, Mohammad K, Jensen, Richard A, Jørgensen, Marit E, Jørgensen, Torben, Karaleftheri, Maria, Khor, Chiea C, Kirkpatrick, Andrea, Kraja, Aldi T, Kuusisto, Johanna, Lange, Ethan M, Lee, IT, Lee, Wen-Jane, Leong, Aaron, Liao, Jiemin, Liu, Chunyu, Liu, Yongmei, Lindgren, Cecilia M, Linneberg, Allan, and Malerba, Giovanni

Subjects
Blood Glucose, European Continental Ancestry Group, Black People, Metabolic and Endocrine, White People, Glucagon-Like Peptide-1 Receptor, Mutation Rate, Clinical Research, Diabetes Mellitus, Genetics, Humans, Insulin, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Exome, Aetiology, Polymorphism, Genetic Association Studies, Oligonucleotide Array Sequence Analysis, African Continental Ancestry Group, Nutrition, Prevention, Diabetes, Human Genome, Genetic Variation, Fasting, Single Nucleotide, Genetic Loci, Glucose-6-Phosphatase, EPIC-InterAct Consortium, Type 2
Abstract

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

Published
2015

9. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

Wessel, Jennifer, Chu, Audrey Y, Willems, Sara M, Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A, Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E, An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J, Grarup, Niels, Ehm, Margaret G, Li, Li, Baldridge, Abigail S, Stančáková, Alena, Abrol, Ravinder, Besse, Céline, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F, Garcia, Melissa E, Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A, Layton, Jill C, Li, Man, Hua Zhao, Jing, Meidtner, Karina, Morrison, Alanna C, Nalls, Mike A, Peters, Marjolein J, Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V, Southam, Lorraine, Stoiber, Marcus H, Strawbridge, Rona J, Taylor, Kent D, and Jørgensen, Torben

Subjects
biological sciences, genetics
Abstract

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

Published
2015
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10. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

Wessel, Jennifer, Chu, Audrey Y, Willems, Sara M, Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A, Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E, An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J, Grarup, Niels, Ehm, Margaret G, Li, Li, Baldridge, Abigail S, Stančáková, Alena, Abrol, Ravinder, Besse, Céline, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F, Garcia, Melissa E, Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A, Layton, Jill C, Li, Man, Hua Zhao, Jing, Meidtner, Karina, Morrison, Alanna C, Nalls, Mike A, Peters, Marjolein J, Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V, Southam, Lorraine, Stoiber, Marcus H, Strawbridge, Rona J, Taylor, Kent D, Varga, Tibor V, and Allin, Kristine H

Subjects
Exome/genetics, SEQUENCING DATA, TRIGLYCERIDE LEVELS, Research Support, American Recovery and Reinvestment Act, Fasting/blood, Mutation Rate, Research Support, N.I.H., Extramural, GLYCEMIC TRAITS, Journal Article, Humans, Genetic Predisposition to Disease, European Continental Ancestry Group/genetics, GENOME-WIDE ASSOCIATION, Genetic Association Studies, Oligonucleotide Array Sequence Analysis, PLASMA-GLUCOSE, INSULIN-RESISTANCE, GLUCAGON-LIKE PEPTIDE-1, Blood Glucose/metabolism, Research Support, Non-U.S. Gov't, African Continental Ancestry Group/genetics, Genetic Variation, Glucagon-Like Peptide-1 Receptor/genetics, GERMLINE MUTATIONS, Polymorphism, Single Nucleotide/genetics, Research Support, N.I.H., Intramural, RECEPTOR GENE, Glucose-6-Phosphatase/genetics, Genetic Loci, CODING VARIATION, Diabetes Mellitus, Type 2/blood, Insulin/blood, Research Support, U.S. Gov't, Non-P.H.S
Abstract

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

Published
2015

11. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

Grarup, Niels, Fox, Keolu, An, Ping, Li, Li, Hivert, Marie-France, Rasmussen-Torvik, Laura J, Lipovich, Leonard, Raghavan, Sridharan, Baldridge, Abigail S, Dauriz, Marco, Huffman, Jennifer E, Besse, Céline, Guo, Xiuqing, Bork-Jensen, Jette, Chu, Audrey Y, Hidalgo, Bertha, Hara, Kazuo, Fornage, Myriam, Yaghootkar, Hanieh, Willems, Sara M, Stančáková, Alena, Wessel, Jennifer, Abrol, Ravinder, Freitag, Daniel F, Wang, Shuai, Jakobsdottir, Johanna, Garcia, Melissa E, Lu, Yingchang, Brody, Jennifer A, Isaacs, Aaron, Boland, Anne, and Ehm, Margaret G

Abstract

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=−0.09±0.01 mmol l−1, P=3.4 × 10−12), T2D risk (OR[95%CI]=0.86[0.76–0.96], P=0.010), early insulin secretion (β=−0.07±0.035 pmolinsulin mmolglucose−1, P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l−1, P=4.3 × 10−4). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10−6) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l−1, P=1.3 × 10−8). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility. Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1R significantly associated with these traits.

Published
2015
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13. New insights on the genetic etiology of Alzheimer’s and related dementia

Author

Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris, Andrade, Victor, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C., Grenier-Boley, Benjamin, Campos-Martin, Rafael, Holmans, Peter A., Boland, Anne, Kleineidam, Luca, Damotte, Vincent, van der Lee, Sven J., Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C., Yaqub, Amber, Prokic, Ivana, Costa, Marcos R, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Boada, Mercè, Aarsland, Dag, García-González, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J., Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Belén Pastor, Ana, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizzarro, Alessandra, Alcolea, Daniel, Blesa, Rafael, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bresner, Catherine, Brookes, Keeley J., Brusco, Luis Ignacio, Bûrger, Katharina, Bullido, María J., Burholt, Vanessa, Bush, William S., Calero, Miguel, Dufouil, Carole, Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chillotti, Caterina, Brodaty, Henry, Ciccone, Simona, Claassen, Jurgen A.H.R., Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D., Debette, Stéphanie, Deckert, Jürgen, del Ser, Teodoro, Denning, Nicola, DeStefano, Anita, Dichgans, Martin, Diehl-Schmid, Janine, Diez-Fairen, Mónica, Rossi, Paolo Dionigi, Djurovic, Srdjan, Duron, Emmanuelle, Düzel, Emrah, Engelborghs, Sebastiaan, Escott-Price, Valentina, Espinosa, Ana, Buiza-Rueda, Dolores, Ewers, Michael, Tagliavini, Fabrizio, Nielsen, Sune Fallgaard, Farotti, Lucia, Fenoglio, Chiara, Fernández-Fuertes, Marta, Hardy, John, Ferrari, Raffaele, Ferreira, Catarina B, Ferri, Evelyn, Fin, Bertrand, Fischer, Peter, Fladby, Tormod, Fließbach, Klaus, Fortea, Juan, Fostinelli, Silvia, Fox, Nick C., Franco-Macías, Emlio, Frank-García, Ana, Froelich, Lutz, Galimberti, Daniela, García-Alberca, Jose Maria, Garcia-Madrona, Sebastian, García-Ribas, Guillermo, Chene, Geneviève, Ghidoni, Roberta, Giegling, Ina, Giaccone, Giorgio, Goldhardt, Oliver, González-Pérez, Antonio, Graff, Caroline, Grande, Giulia, Green, Emma, Grimmer, Timo, Grünblatt, Edna, Guetta-Baranes, Tamar, Haapasalo, Annakaisa, Hadjigeorgiou, Georgios, Haines, Jonathan L., Hamilton-Nelson, Kara L., Hampel, Harald, Hanon, Olivier, Hartmann, Annette M., Hausner, Lucrezia, Harwood, Janet, Heilmann-Heimbach, Stefanie, Helisalmi, Seppo, Heneka, Michael T., Hernández, Isabel, Herrmann, Martin J., Hoffmann, Per, Holmes, Clive, Holstege, Henne, Vilas, Raquel Huerto, Hulsman, Marc, Humphrey, Jack, Biessels, Geert Jan, Johansson, Charlotte, Kehoe, Patrick G., Kilander, Lena, Ståhlbom, Anne Kinhult, Kivipelto, Miia, Koivisto, Anne, Kornhuber, Johannes, Kosmidis, Mary H., Kuksa, Pavel P., Kunkle, Brian W., Lage, Carmen, Laukka, Erika J, Lauria, Alessandra, Lee, Chien-Yueh, Lehtisalo, Jenni, Satizabal, Claudia L., Lerch, Ondrej, Lleó, Alberto, Lopez, Rogelio, Lopez, Oscar, de Munain, Adolfo Lopez, Love, Seth, Löwemark, Malin, Luckcuck, Lauren, Macías, Juan, MacLeod, Catherine A., Maier, Wolfgang, Mangialasche, Francesca, Spallazzi, Marco, Marquié, Marta, Marshall, Rachel, Martin, Eden R., Martín Montes, Angel, Rodríguez, Carmen Martínez, Masullo, Carlo, Mayeux, Richard, Mead, Simon, Mecocci, Patrizia, Medina, Miguel, Meggy, Alun, Mendoza, Silvia, Menéndez-González, Manuel, Mir, Pablo, Periñán, Maria Teresa, Mol, Merel, Molina-Porcel, Laura, Montrreal, Laura, Morelli, Laura, Moreno, Fermín, Morgan, Kevin, Nöthen, Markus M., Muchnik, Carolina, Nacmias, Benedetta, Ngandu, Tiia, Nicolas, Gael, Nordestgaard, Børge G., Olaso, Robert, Orellana, Adelina, Orsini, Michela, Ortega, Gemma, Padovani, Alessandro, Caffarra, Paolo, Papenberg, Goran, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Pérez-Cordón, Alba, Pérez-Tur, Jordi, Pericard, Pierre, Peters, Oliver, Pijnenburg, Yolande A.L., Pineda, Juan A, Piñol-Ripoll, Gerard, Pisanu, Claudia, Polak, Thomas, Popp, Julius, Posthuma, Danielle, Priller, Josef, Puerta, Raquel, Quenez, Olivier, Quintela, Inés, Thomassen, Jesper Qvist, Rábano, Alberto, Rainero, Innocenzo, Ramakers, Inez, Real, Luis M, Reinders, Marcel J.T., Riedel-Heller, Steffi, Riederer, Peter, Rodriguez-Rodriguez, Eloy, Rongve, Arvid, Allende, Irene Rosas, Rosende-Roca, Maitée, Royo, Jose Luis, Rubino, Elisa, Rujescu, Dan, Sáez, María Eugenia, Sakka, Paraskevi, Saltvedt, Ingvild, Sanabria, Ángela, Sánchez-Arjona, María Bernal, Sanchez-Garcia, Florentino, Mehrabian, Shima, Sánchez-Juan, Pascual, Sánchez-Valle, Raquel, Sando, Sigrid B, Scamosci, Michela, Scarmeas, Nikolaos, Scarpini, Elio, Scheltens, Philip, Scherbaum, Norbert, Scherer, Martin, Schmid, Matthias, Schneider, Anja, Schott, Jonathan M., Selbæk, Geir, Sha, Jin, Shadrin, Alexey A, Skrobot, Olivia, Snijders, Gijsje J. L., Soininen, Hilkka, Solfrizzi, Vincenzo, Solomon, Alina, Sorbi, Sandro, Sotolongo-Grau, Oscar, Spalletta, Gianfranco, Spottke, Annika, Squassina, Alessio, Tartari, Juan Pablo, Tárraga, Lluís, Tesí, Niccolo, Thalamuthu, Anbupalam, Tegos, Thomas, Traykov, Latchezar, Tremolizzo, Lucio, Tybjærg-Hansen, Anne, Uitterlinden, Andre, Ullgren, Abbe, Ulstein, Ingun, Valero, Sergi, Van Broeckhoven, Christine, van der Lugt, Aad, Van Dongen, Jasper, van Rooij, Jeroen, van Swieten, John, Vandenberghe, Rik, Verhey, Frans, Vidal, Jean-Sébastien, Vogelgsang, Jonathan, Vyhnalek, Martin, Wagner, Michael, Wallon, David, Wang, Li-San, Wang, Ruiqi, Weinhold, Leonie, Wiltfang, Jens, Windle, Gill, Woods, Bob, Yannakoulia, Mary, Zhao, Yi, Zulaica, Miren, Serrano-Rios, Manuel, Seripa, Davide, Stordal, Eystein, Farrer, Lindsay A., Psaty, Bruce M., Ghanbari, Mohsen, Raj, Towfique, Sachdev, Perminder, Mather, Karen, Jessen, Frank, Ikram, M. Arfan, de Mendonça, Alexandre, Hort, Jakub, Tsolaki, Magda, Pericak-Vance, Margaret A., Amouyel, Philippe, Williams, Julie, Frikke-Schmidt, Ruth, Clarimon, Jordi, Deleuze, Jean-François, Rossi, Giacomina, Seshadri, Sudha, Andreassen, Ole A., Ingelsson, Martin, Hiltunen, Mikko, Sleegers, Kristel, Schellenberg, Gerard D., van Duijn, Cornelia M., Sims, Rebecca, van der Flier, Wiesje M., Ruiz, Agustín, Ramirez, Alfredo, and Lambert, Jean-Charles

Subjects
0303 health sciences, Microglia, Amyloid, business.industry, Disease, medicine.disease, Bioinformatics, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Genetic etiology, Medicine, Dementia, Egfr signaling, business, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract

Alzheimer’s disease (AD) is a severe and incurable neurodegenerative disease, and the failure to find effective treatments suggests that the underlying pathology remains poorly understood. Due to its strong heritability, deciphering the genetic landscape of AD and related dementia (ADD) is a unique opportunity to advance our knowledge. We completed a meta-analysis of genome-wide association studies (39,106 clinically AD-diagnosed cases, 46,828 proxy-ADD cases and 401,577 controls) with the most promising signals followed-up in 25,392 independent AD cases and 276,086 controls. We report 75 risk loci for ADD, including 42 novel ones. Pathway-enrichment analyses confirm the involvement of amyloid/Tau pathways, highlight the role of microglia and its potential interaction with APP metabolism. Numerous genes exhibited differential expression or splicing in AD-related conditions and gene prioritization implies EGFR signaling and TNF-α pathway through LUBAC complex. We also generated a novel polygenic risk score strongly associated with the risk of future dementia or progression from mild cognitive impairment to dementia. In conclusion, by more than doubling the number of loci associated with ADD risk, our study offers new insights into the pathophysiological processes underlying AD and offers additional therapeutic entry-points and tools for translational genomics.

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14. A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus

Author

Mobuchon, Lenha, Battistella, Aude, Bardel, Claire, Scelo, Ghislaine, Renoud, Alexia, Houy, Alexandre, Cassoux, Nathalie, Milder, Maud, Cancel-Tassin, Géraldine, Cussenot, Olivier, Delattre, Olivier, Besse, Céline, Boland, Anne, Deleuze, Jean-François, Cox, David G., and Stern, Marc-Henri

Subjects
Genetics, Medicine, sense organs, QH426-470, eye diseases, Article
Abstract

Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43–2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis., Cancer: Risk allele identified for melanoma of the eye Researchers have discovered an important genetic risk variant linked to uveal melanoma, a rare malignant tumor of the eye. Marc-Henri Stern from Institut Curie in Paris, France, and colleagues compared more than 860,000 single DNA variants covering the entire genome, from the genomes of 259 people with uveal melanoma and 401 healthy controls, all of whom were of European ancestry. The researchers found that a series of closely linked gene variants on the short arm of chromosome 5 were significantly more common in the melanoma patients. They confirmed the association between this genomic region and disease risk in an independent cohort of 276 cancer cases and 184 controls. Expression analyses showed that the CLPTM1L gene contained in this region was more expressed in people with the risk variants, pointing to CLPTM1L playing a role in tumor development.

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