Academic Journal
Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes
| العنوان: | Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes |
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| المؤلفون: | Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel, Allen, Jamie, Kar, Siddhartha, Pooley, Karen, Dennis, Joe, Michailidou, Kyriaki, Turman, Constance, Soucy, Penny, Lemaçon, Audrey, Lush, Michael, Tyrer, Jonathan, Ghoussaini, Maya, Moradi Marjaneh, Mahdi, Jiang, Xia, Agata, Simona, Aittomäki, Kristiina, Alonso, M Rosario, Andrulis, Irene, Anton-Culver, Hoda, Antonenkova, Natalia, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan, Arun, Banu, Auber, Bernd, Auer, Paul, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa, Barrowdale, Daniel, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blanco, Amie, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Stig, Bolla, Manjeet, Bonanni, Bernardo, Borg, Ake, Bosse, Kristin, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brock, Ian, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria, Camp, Nicola, Campbell, Ian, Canzian, Federico, Carroll, Jason, Carter, Brian, Castelao, Jose, Chiquette, Jocelyne, Christiansen, Hans, Chung, Wendy, Claes, Kathleen, Clarke, Christine, Collée, J Margriet, Cornelissen, Sten, Couch, Fergus, Cox, Angela, Cross, Simon, Cybulski, Cezary, Czene, Kamila, Daly, Mary, de La Hoya, Miguel, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Dite, Gillian, Domchek, Susan, Dörk, Thilo, Dos-Santos-Silva, Isabel, Droit, Arnaud, Dubois, Stéphane, Dumont, Martine, Duran, Mercedes, Durcan, Lorraine, Dwek, Miriam, Eccles, Diana, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter, Fletcher, Olivia, Floris, Giuseppe, Flyger, Henrik, Foretova, Lenka, Foulkes, William, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gabrielson, Marike, Gago-Dominguez, Manuela, Gambino, Gaetana, Ganz, Patricia, Gapstur, Susan, Garber, Judy, García-Sáenz, José, Gaudet, Mia, Georgoulias, Vassilios, Giles, Graham, Glendon, Gord, Godwin, Andrew, Goldberg, Mark, Goldgar, David, González-Neira, Anna, Tibiletti, Maria Grazia, Greene, Mark, Grip, Mervi, Gronwald, Jacek, Grundy, Anne, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher, Håkansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia, Hartikainen, Jaana, Hartman, Mikael, He, Wei, Healey, Catherine, Heemskerk-Gerritsen, Bernadette, Heyworth, Jane, Hillemanns, Peter, Hogervorst, Frans, Hollestelle, Antoinette, Hooning, Maartje, Hopper, John, Howell, Anthony, Huang, Guanmengqian, Hulick, Peter, Imyanitov, Evgeny, Isaacs, Claudine, Iwasaki, Motoki, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jankowitz, Rachel, John, Esther, Johnson, Nichola, Jones, Michael, Jukkola-Vuorinen, Arja, Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Kapoor, Pooja Middha, Karlan, Beth, Keeman, Renske, Kerin, Michael, Khusnutdinova, Elza, Kiiski, Johanna, Kirk, Judy, Kitahara, Cari, Ko, Yon-Dschun, Konstantopoulou, Irene, Kosma, Veli-Matti, Koutros, Stella, Kubelka-Sabit, Katerina, Kwong, Ava, Kyriacou, Kyriacos, Laitman, Yael, Lambrechts, Diether, Lee, Eunjung, Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Lindblom, Annika, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer, Lubiński, Jan, Macinnis, Robert, Maishman, Tom, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Mayes, Rebecca, Mcguffog, Lesley, Mclean, Catriona, Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Miller, Nicola, Montagna, Marco, Moreno, Fernando, Muir, Kenneth, Mulligan, Anna Marie, Muñoz-Garzon, Victor, Muranen, Taru, Narod, Steven, Nassir, Rami, Nathanson, Katherine, Neuhausen, Susan, Nevanlinna, Heli, Neven, Patrick, Nielsen, Finn, Nikitina-Zake, Liene, Norman, Aaron, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo, Olsson, Håkan, Orr, Nick, Osorio, Ana, Pankratz, V Shane, Papp, Janos, Park, Sue, Park-Simon, Tjoung-Won, Parsons, Michael, Paul, James, Pedersen, Inge Sokilde, Peissel, Bernard, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Presneau, Nadege, Prokofyeva, Darya, Pujana, Miquel Angel, Pylkäs, Katri, Radice, Paolo, Ramus, Susan, Rantala, Johanna, Rau-Murthy, Rohini, Rennert, Gad, Risch, Harvey, Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sánchez-Herrero, Estela, Sandler, Dale, Santamariña, Marta, Saunders, Christobel, Sawyer, Elinor, Scheuner, Maren, Schmidt, Daniel, Schmutzler, Rita, Schneeweiss, Andreas, Schoemaker, Minouk, Schöttker, Ben, Schürmann, Peter, Scott, Christopher, Scott, Rodney, Senter, Leigha, Seynaeve, Caroline, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Singer, Christian, Slavin, Thomas, Smichkoska, Snezhana, Southey, Melissa, Spinelli, John, Spurdle, Amanda, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony, Tamimi, Rulla, Tan, Yen Yen, Tapper, William, Taylor, Jack, Teixeira, Manuel, Tengström, Maria, Teo, Soo Hwang, Terry, Mary Beth, Teulé, Alex, Thomassen, Mads, Thull, Darcy, Tischkowitz, Marc, Toland, Amanda, Tollenaar, Rob, Tomlinson, Ian, Torres, Diana, Torres-Mejía, Gabriela, Troester, Melissa, Truong, Thérèse, Tung, Nadine, Tzardi, Maria, Ulmer, Hans-Ulrich, Vachon, Celine, van Asperen, Christi, van Der Kolk, Lizet, van Rensburg, Elizabeth, Vega, Ana, Viel, Alessandra, Vijai, Joseph, Vogel, Maartje, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice, Weitzel, Jeffrey, Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Wu, Anna, Yannoukakos, Drakoulis, Zhang, Yan, Zheng, Wei, Hunter, David, Pharoah, Paul, Chang-Claude, Jenny, García-Closas, Montserrat, Schmidt, Marjanka, Milne, Roger, Kristensen, Vessela, French, Juliet, Edwards, Stacey, Antoniou, Antonis, Chenevix-Trench, Georgia, Simard, Jacques, Easton, Douglas, Kraft, Peter, Dunning, Alison, Alonso, M. Rosario, Collée, J. Margriet, Evans, D. Gareth, Pankratz, V. Shane |
| المساهمون: | University of Cambridge UK (CAM), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS), Harvard T.H. Chan School of Public Health, QIMR Berghofer Medical Research Institute, University of Cyprus Nicosia (UCY), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Curie Paris, Fondation MINES ParisTech, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation), the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492), and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note., We thank all of the individuals who took part in these studies, as well as all of the researchers, clinicians, technicians and administrative staff who enabled this work to be carried out., GEMO Study Collaborators Véronique Mari, Pascaline Berthet, Laurent Castera, Dominique Vaur, Hakima Lallaoui, Yves-Jean Bignon, Nancy Uhrhammer, Valérie Bonadona, Christine Lasset, Françoise Révillion, Paul Vennin, Daniele Muller, Denise Molina Gomes, Olivier Ingster, Isabelle Coupier, Pascal Pujol, Marie-Agnès Collonge-Rame, Isabelle Mortemousque, Odile Bera, Mickaelle Rose, Amandine Baurand, Geoffrey Bertolone, Laurence Faivre, Hélène Dreyfus, Dominique Leroux, Laurence Venat-Bouvet, Stéphane Bézieau, Capucine Delnatte, Jean Chiesa, Brigitte Gilbert-Dussardier, Paul Gesta, Fabienne Prieur Prieur, Myriam Bronner, Johanna Sokolowska, Florence Coulet, Nadia Boutry-Kryza, Alain Calender, Sophie Giraud, Mélanie Leone, Sandra Fert-Ferrer, Dominique Stoppa-Lyonnet, Yue Jiao, Fabienne Lesueur Lesueur, Noura Mebirouk, Emmanuelle Barouk-Simonet, Virginie Bubien, Michel Longy, Nicolas Sevenet, Laurence Gladieff, Christine Toulas, Audrey Reimineras, Hagay Sobol, Brigitte Bressac-de Paillerets, Odile Cabaret, Olivier Caron, Marine Guillaud-Bataille, Etienne Rouleau, Muriel Belotti, Bruno Buecher, Sandrine Caputo, Chrystelle Colas, Antoine De Pauw, Emmanuelle Fourme, Marion Gauthier-Villars, Lisa Golmard, Virginie Moncoutier & Claire Saule, EMBRACE Collaborators Alan Donaldson, Alex Murray, Angela Brady, Carole Brewer, Caroline Pottinger, Clare Miller, David Gallagher, Helen Gregory, Jackie Cook, Jacqueline Eason, Julian Adlard, Julian Barwell, Kai-Ren Ong, Katie Snape, Lisa Walker, Louise Izatt, Lucy Side, Marc Tischkowitz, Mark T. Rogers, Mary E. Porteous, Munaza Ahmed, Patrick J. Morrison, Paul Brennan, Ros Eeles & Rosemarie Davidson, European Project: 656144,H2020,H2020-MSCA-IF-2014,RADIOGENFF(2016), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015) |
| المصدر: | ISSN: 1061-4036. |
| بيانات النشر: | CCSD Nature Publishing Group |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | MESH: Bayes Theorem, MESH: Biomarkers, Tumor, MESH: Risk Factors, MESH: Breast Neoplasms, MESH: Chromosome Mapping, MESH: Female, MESH: Genetic Predisposition to Disease, MESH: Genome-Wide Association Study, MESH: Humans, MESH: Linkage Disequilibrium, MESH: Polymorphism, Single Nucleotide, MESH: Quantitative Trait Loci, MESH: Regulatory Sequences, Nucleic Acid, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [STAT.ME]Statistics [stat]/Methodology [stat.ME], [STAT.AP]Statistics [stat]/Applications [stat.AP], [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] |
| الوصف: | International audience ; Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/31911677; info:eu-repo/grantAgreement//656144/EU/RADIOGENOMICS: Finding Genetic Functional Variants Through Fine Mapping/RADIOGENFF; info:eu-repo/grantAgreement/EC/FP7/223175/EU/Collaborative Oncological Gene-environment Study/COGS; info:eu-repo/grantAgreement//633784/EU/Breast CAncer STratification: understanding the determinants of risk and prognosis of molecular subtypes/B-CAST; info:eu-repo/grantAgreement//634935/EU/Breast Cancer Risk after Diagnostic Gene Sequencing (BRIDGES)/BRIDGES; PUBMED: 31911677; PUBMEDCENTRAL: PMC6974400 |
| DOI: | 10.1038/s41588-019-0537-1 |
| الاتاحة: | https://pasteur.hal.science/pasteur-03278553 https://pasteur.hal.science/pasteur-03278553v1/document https://pasteur.hal.science/pasteur-03278553v1/file/EMS84721.pdf https://doi.org/10.1038/s41588-019-0537-1 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.64A990FB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41588-019-0537-1 |
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