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L. Fachal, H. Aschard, J. Beesley, D. Barnes, Jamie Allen, S. Kar, K. Pooley, J. Dennis, K. Michailidou, Constance Turman, P. Soucy, Audrey Lemaçon, M. Lush, J. Tyrer, M. Ghoussaini, M. Moradi Marjaneh, Xia Jiang, S. Agata, K. Aittomäki, M. Alonso, I. Andrulis, H. Anton-Culver, N. Antonenkova, A. Arason, V. Arndt, K. Aronson, B. Arun, B. Auber, P. Auer, J. Azzollini, J. Balmaña, R. Barkardottir, D. Barrowdale, A. Beeghly-Fadiel, J. Benítez, M. Bermisheva, K. Białkowska, Amie M. Blanco, C. Blomqvist, W. Blot, N. Bogdanova, S. Bojesen, M. Bolla, B. Bonanni, Å. Borg, K. Bosse, H. Brauch, H. Brenner, I. Briceño, I. Brock, A. Brooks-Wilson, T. Brüning, B. Burwinkel, S. Buys, Q. Cai, T. Caldés, M. Caligo, N. Camp, Ian Campbell, F. Canzian, J. Carroll, B. Carter, J. Castelao, J. Chiquette, H. Christiansen, W. Chung, K. Claes, Christine L. Clarke, Véronique Pascaline Laurent Dominique Hakima Yves-Jean Nancy Mari Berthet Castera Vaur Lallaoui Bignon Uhrhamme, V. Mari, P. Berthet, L. Castéra, D. Vaur, H. Lallaoui, Y. Bignon, N. Uhrhammer, V. Bonadona, C. Lasset, F. Révillion, P. Vennin, D. Muller, D. M. Gomes, O. Ingster, I. Coupier, P. Pujol, M. Collonge-Rame, Isabelle Mortemousque, O. Béra, Mickaelle Rose, A. Baurand, G. Bertolone, L. Faivre, H. Dreyfus, D. Leroux, L. Venat-Bouvet, S. Bézieau, Capucine Delnatte, J. Chiésa, B. Gilbert-Dussardier, P. Gesta, F. Prieur, M. Bronner, Johanna Sokolowska, F. Coulet, N. Boutry‐Kryza, A. Calender, S. Giraud, M. Léoné, S. Fert‐Ferrer, D. Stoppa-Lyonnet, Y. Jiao, F. Lesueur, Noura Mebirouk, E. Barouk-Simonet, V. Bubien, M. Longy, N. Sevenet, L. Gladieff, C. Toulas, Audrey Reimineras, H. Sobol, B. Paillerets, O. Cabaret, O. Caron, M. Guillaud-Bataille, E. Rouleau, Muriel Belotti, B. Buecher, S. Caputo, C. Colas, A. Pauw, E. Fourme, M. Gauthier‐Villars, L. Golmard, V. Moncoutier, C. Saule, Alan Alex Angela Carole Caroline Clare David Helen Jack Donaldson Murray Brady Brewer Pottinger Miller Gal, A. Donaldson, A. Murray, A. Brady, C. Brewer, C. Pottinger, Clare B Miller, D. Gallagher, H. Gregory, J. Cook, J. Eason, J. Adlard, J. Barwell, K. Ong, K. Snape, L. Walker, L. Izatt, L. Side, M. Tischkowitz, M. Rogers, M. Porteous, Munaza Ahmed, P. Morrison, P. Brennan, R. Eeles, R. Davidson, J. Collée, S. Cornelissen, F. Couch, A. Cox, S. Cross, C. Cybulski, K. Czene, M. Daly, M. de la Hoya, P. Devilee, O. Díez, Y. Ding, G. Dite, S. Domchek, T. Dörk, I. dos-Santos-Silva, Arnaud Droit, S. Dubois, M. Dumont, M. Durán, L. Durcan, M. Dwek, D. Eccles, C. Engel, M. Eriksson, D. Evans, P. Fasching, O. Fletcher, G. Floris, H. Flyger, L. Foretova, W. Foulkes, E. Friedman, L. Fritschi, D. Frost, M. Gabrielson, M. Gago-Domínguez, G. Gambino, P. Ganz, S. Gapstur, J. Garber, J. García-Saenz, M. Gaudet, V. Georgoulias, G. Giles, G. Glendon, A. Godwin, M. Goldberg, D. Goldgar, A. González-Neira, M. Tibiletti, M. Greene, Mervi Grip, J. Gronwald, Anne Grundy, P. Guénel, E. Hahnen, C. Haiman, N. Håkansson, P. Hall, U. Hamann, P. Harrington, Jaana M. Hartikainen, M. Hartman, Wei He, C. Healey, B. Heemskerk-Gerritsen, J. Heyworth, P. Hillemanns, Frans B. L. Hogervorst, A. Hollestelle, M. Hooning, J. Hopper, A. Howell, Guanmengqian Huang, P. Hulick, E. Imyanitov, Adrienne Alice Alison Allan Andrew Andrew Anna De Anneke As Sexton Christian Trainer Spigelman Fellows Shellin, A. Sexton, Alice Christian, A. Trainer, A. Spigelman, A. Fellows, A. Shelling, A. Fazio, A. Blackburn, A. Crook, B. Meiser, B. Patterson, Christine L. Clarke, Christobel Saunders, C. Hunt, C. Scott, D. Amor, Deb Marsh, E. Edkins, E. Salisbury, E. Haan, Eveline Neidermayr, F. Macrea, G. Farshid, G. Lindeman, G. Trench, G. Mann, G. Giles, G. Gill, H. Thorne, Ian Campbell, I. Hickie, I. Winship, J. Flanagan, J. Kollias, J. Visvader, J. Stone, Jessica Taylor, J. Burke, J. Saunus, J. Forbes, J. Hopper, J. Beesley, Judy Kirk, J. French, K. Tucker, Kathy Wu, K. Phillips, L. Lipton, Leslie H. Andrews, Lizz Lobb, Logan C. Walker, Maira Kentwell, M. Spurdle, M. Cummings, M. Gleeson, M. Harris, M. Jenkins, M. Young, M. Delatycki, M. Wallis, Matthew Burgess, M. Price, Melissa A. Brown, M. Southey, M. Bogwitz, M. Field, M. Friedlander, M. Gattas, M. Saleh, N. Hayward, N. Pachter, Paul Cohen, Pascal H. G. Duijf, Paul A. James, Peter Simpson, P. Fong, P. Butow, Rachael Williams, R. Kefford, Rodney J. Scott, R. Milne, R. Balleine, S. Dawson, S. Lok, S. O’Connell, Sian Greening, S. Nightingale, S. Edwards, S. Fox, S. McLachlan, S. Lakhani, Y. Antill, Cora Hanne Klaartje Hans Ingrid Margriet Carolien Maart Aalfs Meijers-Heijboer van Engelen Gille Boere Col, C. Aalfs, H. Meijers-Heijboer, K. van Engelen, H. Gille, I. Boere, M. Collée, C. V. van Deurzen, M. Hooning, I. Obdeijn, A. V. D. van den Ouweland, C. Seynaeve, S. Siesling, J. Verloop, C. V. van Asperen, P. Devilee, T. van Cronenburg, Rien Blok, M. de Boer, E. García, M. Adank, Frans B. L. Hogervorst, D. Jenner, F. V. van Leeuwen, M. Rookus, N. Russell, M. Schmidt, Sandra van den Belt-Dusebout, C. Kets, A. Mensenkamp, T. D. de Bock, A. H. van der Hout, M. Mourits, J. Oosterwijk, M. Ausems, M. Koudijs, Christine Deborah Rodney Robert Desmond Jane Alison Nirmala Clarke Marsh Scott Baxter Yip Carpenter Davis Path, Christine L. Clarke, Deb Marsh, Rodney J. Scott, R. Baxter, D. Yip, Jane E. Carpenter, Alison Davis, N. Pathmanathan, Peter Simpson, Dinny Graham, Mythily Sachchithananthan, C. Isaacs, M. Iwasaki, A. Jager, M. Jakimovska, A. Jakubowska, Paul A. James, R. Janavicius, R. Jankowitz, E. John, N. Johnson, Michael E. Jones, A. Jukkola-Vuorinen, A. Jung, R. Kaaks, D. Kang, P. Kapoor, B. Karlan, R. Keeman, M. Kerin, E. Khusnutdinova, J. Kiiski, Judy Kirk, C. Kitahara, Y. Ko, I. Konstantopoulou, V. Kosma, Stella Koutros, Katerina Kubelka-Sabit, A. Kwong, K. Kyriacou, Y. Laitman, D. Lambrechts, Eunjung Lee, Goska Leslie, J. Lester, F. Lesueur, A. Lindblom, W. Lo, J. Long, A. Lophatananon, J. Loud, J. Lubiński, R. MacInnis, T. Maishman, E. Makalic, A. Mannermaa, M. Manoochehri, S. Manoukian, S. Margolin, M. Martínez, K. Matsuo, T. Maurer, D. Mavroudis, R. Mayes, L. McGuffog, C. Mclean, Noura Mebirouk, A. Meindl, Austin Miller, N. Miller, M. Montagna, F. Moreno, K. Muir, A. Mulligan, V. Munoz-Garzon, T. Muranen, S. Narod, R. Nassir, K. Nathanson, S. Neuhausen, H. Nevanlinna, P. Neven, F. Nielsen, L. Nikitina-Zake, A. Norman, K. Offit, E. Oláh, O. Olopade, H. Olsson, N. Orr, A. Osorio, V. Pankratz, J. Papp, Sue-Kyung Park, T. Park-Simon, M. Parsons, J. Paul, I. Pedersen, B. Peissel, B. Peshkin, P. Peterlongo, J. Peto, D. Plaseska‐Karanfilska, Karolina Prajzendanc, R. Prentice, N. Presneau, D. Prokofyeva, M. Pujana, K. Pylkäs, P. Radice, S. Ramus, Johanna Rantala, R. Rau‐Murthy, G. Rennert, H. Risch, M. Robson, A. Romero, M. Rossing, E. Saloustros, E. Sánchez-Herrero, D. Sandler, M. Santamariña, Christobel Saunders, E. Sawyer, M. Scheuner, D. Schmidt, R. Schmutzler, A. Schneeweiss, M. Schoemaker, B. Schöttker
143 25. 10. 2019.

Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

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. Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.


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