Year: 2019
Type: Article
Title: Fine-mapping of 150 breast cancer risk regions identifies 178 high confidence target genes
Author: Fachal, Laura
Author: Aschard, Hugues
Author: Beesley, Jonathan
Author: Barnes, Daniel
Author: Allen, Jamie
Author: Kar, Siddhartha
Author: Pooley, Karen
Author: Dennis, Joe
Author: Michailidou, Kyriaki
Author: Turman, Constance
Author: Soucy, Penny
Author: Lemacon, Audrey
Author: Lush, Michael
Author: Tyrer, Jonathan
Author: Ghoussaini, Maya
Author: Moradi Marjaneh, Mahdi
Author: Jiang, Xia
Author: Agata, Simona
Author: Aittomaki, Kristiina
Author: Alonso, M. Rosario
Author: Andrulis, Irene
Author: Anton-Culver, Hoda
Author: Antonenkova, Natalia
Author: Arason, Adalgeir
Author: Arndt, Volker
Author: Aronson, Kristan
Author: Arun, Banu
Author: Auber, Bernd
Author: Auer, Paul
Author: Azzollini, Jacopo
Author: Balmana, Judith
Author: Barkardottir, Rosa
Author: Barrowdale, Daniel
Author: Beeghly-Fadiel, Alicia
Author: Benitez, Javier
Author: Bermisheva, Marina
Author: Bialkowska, Katarzyna
Author: Blanco, Amie
Author: Blomqvist, Carl
Author: Blot, William
Author: Bogdanova, Natalia
Author: Bojesen, Stig
Author: Bolla, Manjeet
Author: Bonanni, Bernardo
Author: Borg, Ake
Author: Bosse, Kristin
Author: Brauch, Hiltrud
Author: Brenner, Hermann
Author: Briceno, Ignacio
Author: Brock, Ian
Author: Brooks-Wilson, Angela
Author: Bruning, Thomas
Author: Burwinkel, Barbara
Author: Buys, Saundra
Author: Cai, Qiuyin
Author: Caldes, Trinidad
Author: Caligo, Maria
Author: Camp, Nicola
Author: Campbell, Ian
Author: Canzian, Federico
Author: Carroll, Jason
Author: Carter, Brian
Author: Castelao, Jose
Author: Chiquette, Jocelyne
Author: Christiansen, Hans
Author: Chung, Wendy
Author: Claes, Kathleen
Author: Clarke, Christine
Author: Collee, J. Margriet
Author: Cornelissen, Sten
Author: Couch, Fergus
Author: Cox, Angela
Author: Cross, Simon
Author: Cybulski, Cezary
Author: Czene, Kamila
Author: Daly, Mary
Author: de la Hoya, Miguel
Author: Devilee, Peter
Author: Diez, Orland
Author: Ding, Yuan Chun
Author: Dite, Gillian
Author: Domchek, Susan
Author: Dork, Thilo
Author: dos-Santos-Silva, Isabel
Author: Droit, Arnaud
Author: Dubois, Stephane
Author: Dumont, Martine
Author: Duran, Mercedes
Author: Durcan, Lorraine
Author: Dwek, Miriam
Author: Eccles, Diana
Author: Engel, Christoph
Author: Eriksson, Mikael
Author: Evans, D. Gareth
Author: Fasching, Peter
Author: Fletcher, Olivia
Author: Floris, Giuseppe
Author: Flyger, Henrik
Author: Foretova, Lenka
Author: Foulkes, William
Author: Friedman, Eitan
Author: Fritschi, Lin
Author: Frost, Debra
Author: Gabrielson, Marike
Author: Gago-Dominguez, Manuela
Author: Gambino, Gaetana
Author: Ganz, Patricia
Author: Gapstur, Susan
Author: Garber, Judy
Author: Garcia-Saenz, Jose
Author: Gaudet, Mia
Author: Georgoulias, Vassilios
Author: Giles, Graham
Author: Glendon, Gord
Author: Godwin, Andrew
Author: Goldberg, Mark
Author: Goldgar, David
Author: Gonzalez-Neira, Anna
Author: Greene, Mark
Author: Grip, Mervi
Author: Gronwald, Jacek
Author: Grundy, Anne
Author: Guenel, Pascal
Author: Hahnen, Eric
Author: Haiman, Christopher
Author: Hakansson, Niclas
Author: Hall, Per
Author: Hamann, Ute
Author: Harrington, Patricia
Author: Hartikainen, Jaana
Author: Hartman, Mikael
Author: He, Wei
Author: Healey, Catherine
Author: Heemskerk-Gerritsen, Bernadette
Author: Heyworth, Jane
Author: Hillemanns, Peter
Author: Hogervorst, Frans
Author: Hollestelle, Antoinette
Author: Hooning, Maartje
Author: Hopper, John
Author: Howell, Anthony
Author: Huang, Guanmengqian
Author: Hulick, Peter
Author: Imyanitov, Evgeny
Author: Isaacs, Claudine
Author: Iwasaki, Motoki
Author: Jager, Agnes
Author: Jakimovska, Milena
Author: Jakubowska, Anna
Author: James, Paul
Author: Janavicius, Ramunas
Author: Jankowitz, Rachel
Author: John, Esther
Author: Johnson, Nichola
Author: Jones, Michael
Author: Jukkola-Vuorinen, Arja
Author: Jung, Audrey
Author: Kaaks, Rudolf
Author: Kang, Daehee
Author: Karlan, Beth
Author: Keeman, Renske
Author: Kerin, Michael
Author: Khusnutdinova, Elza
Author: Kiiski, Johanna
Author: Kirk, Judy
Author: Kitahara, Cari
Author: Ko, Yon-Dschun
Author: Konstantopoulou, Irene
Author: Kosma, Veli-Matti
Author: Koutros, Stella
Author: Kubelka-Sabit, Katerina
Author: Kwong, Ava
Author: Kyriacou, Kyriacos
Author: Laitman, Yael
Author: Lambrechts, Diether
Author: Lee, Eunjung
Author: Leslie, Goska
Author: Lester, Jenny
Author: Lesueur, Fabienne
Author: Lindblom, Annika
Author: Lo, Wing-Yee
Author: Long, Jirong
Author: Lophatananon, Artitaya
Author: Loud, Jennifer
Author: Lubinski, Jan
Author: MacInnis, Robert
Author: Maishman, Tom
Author: Makalic, Enes
Author: Mannermaa, Arto
Author: Manoochehri, Mehdi
Author: Manoukian, Siranoush
Author: Margolin, Sara
Author: Martinez, Maria Elena
Author: Matsuo, Keitaro
Author: Maurer, Tabea
Author: Mavroudis, Dimitrios
Author: Mayes, Rebecca
Author: McGuffog, Lesley
Author: McLean, Catriona
Author: Mebirouk, Noura
Author: Meindl, Alfons
Author: Middha, Pooja
Author: Miller, Nicola
Author: Miller, Austin
Author: Montagna, Marco
Author: Moreno, Fernando
Author: Mulligan, Anna Marie
Author: Munoz-Garzon, Victor
Author: Muranen, Taru
Author: Narod, Steven
Author: Nassir, Rami
Author: Nathanson, Katherine
Author: Neuhausen, Susan
Author: Nevanlinna, Heli
Author: Neven, Patrick
Author: Nielsen, Finn
Author: Nikitina-Zake, Liene
Author: Norman, Aaron
Author: Offit, Kenneth
Author: Olah, Edith
Author: Olopade, Olufunmilayo
Author: Olsson, Hakan
Author: Orr, Nick
Author: Osorio, Ana
Author: Pankratz, V. Shane
Author: Papp, Janos
Author: Park, Sue
Author: Park-Simon, Tjoung-Won
Author: Parsons, Michael
Author: Paul, James
Author: Pedersen, Inge Sokilde
Author: Peissel, Bernard
Author: Peshkin, Beth
Author: Peterlongo, Paolo
Author: Peto, Julian
Author: Plaseska-Karanfilska, Dijana
Author: Prajzendanz, Karolina
Author: Prentice, Ross
Author: Presneau, Nadege
Author: Prokofyeva, Darya
Author: Pujana, Miquel Angel
Author: Pylkas, Katri
Author: Radice, Paolo
Author: Ramus, Susan
Author: Rantala, Johanna
Author: Rau-Murthy, Rohini
Author: Rennert, Gad
Author: Risch, Harvey
Author: Robson, Mark
Author: Romero, Atocha
Author: Rossing, Caroline Maria
Author: Saloustros, Emmanouil
Author: Sanchez-Herrero, Estela
Author: Sandler, Dale
Author: Santamarina, Marta
Author: Saunders, Christobel
Author: Sawyer, Elinor
Author: Scheuner, Maren
Author: Schmidt, Daniel
Author: Schmutzler, Rita
Author: Schneeweiss, Andreas
Author: Schoemaker, Minouk
Author: Schottker, Ben
Author: Schurmann, Peter
Author: Scott, Christopher
Author: Scott, Rodney
Author: Senter, Leigha
Author: Seynaeve, Caroline
Author: Shah, Mitul
Author: Sharma, Priyanka
Author: Shen, Chen-Yang
Author: Shu, Xiao-Ou
Author: Singer, Christian
Author: Slavin, Thomas
Author: Smichkoska, Snezhana
Author: Southey, Melissa
Author: Spinelli, John
Author: Spurdle, Amanda
Author: Stone, Jennifer
Author: Stoppa-Lyonnet, Dominique
Author: Sutter, Christian
Author: Swerdlow, Anthony
Author: Tamimi, Rulla
Author: Tan, Yen Yen
Author: Tapper, William
Author: Taylor, Jack
Author: Teixeira, Manuel
Author: Tengstrom, Maria
Author: Teo, Soo
Author: Terry, Mary Beth
Author: Teule, Alex
Author: Thomassen, Mads
Author: Thull, Darcy
Author: Tibiletti, Maria Grazia
Author: Tischkowitz, Marc
Author: Toland, Amanda
Author: Tollenaar, Rob
Author: Tomlinson, Ian
Author: Torres, Diana
Author: Torres-Mejia, Gabriela
Author: Troester, Melissa
Author: Tung, Nadine
Author: Tzardi, Maria
Author: Ulmer, Hans-Ulrich
Author: Vachon, Celine
Author: van Asperen, Christi
Author: van der Kolk, Lizet
Author: van Rensburg, Elizabeth
Author: Vega, Ana
Author: Viel, Alessandra
Author: Vijai, Joseph
Author: Vogel, Maatje
Author: Wang, Qin
Author: Wappenschmidt, Barbara
Author: Weinberg, Clarice
Author: Weitzel, Jeffrey
Author: Wendt, Camilla
Author: Wildiers, Hans
Author: Winqvist, Robert
Author: Wolk, Alicja
Author: Wu, Anna
Author: Yannoukakos, Drakoulis
Author: Zhang, Yan
Author: Zheng, Wei
Author: Pharoah, Paul
Author: Chang-Claude, Jenny
Author: Garcia-Closas, Montserrat
Author: Schmidt, Marjanka
Author: Milne, Roger
Author: Kristensen, Vessela
Author: French, Juliet
Author: Edwards, Stacey
Author: Antoniou, Antonis
Author: Chenevix-Trench, Georgia
Author: Simard, Jacques
Author: Easton, Douglas
Author: Kraft, Peter
Author: Dunning, Alison
Author: null, null
Author: null, null
Author: null, null
Author: null, null
Author: null, null
Abstract: 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 (CCVs) 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 (HPPs) 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 potentially causal variants, using gene expression (eQTL), 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 178 highest confidence target genes.
Publisher: Cold Spring Harbor Laboratory
Relation:
Identifier: oai:repository.ukim.mk:20.500.12188/7247
Identifier: http://hdl.handle.net/20.500.12188/7247Identifier: 10.1101/521054
Identifier: https://syndication.highwire.org/content/doi/10.1101/521054
