Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12188/8929
Title: Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses
Authors: Zhang, Haoyu
Ahearn, Thomas U
Lecarpentier, Julie
Barnes, Daniel
Beesley, Jonathan
Qi, Guanghao
Jiang, Xia
O'Mara, Tracy A
Zhao, Ni
Bolla, Manjeet K
Dunning, Alison M
Dennis, Joe
Wang, Qin
Ful, Zumuruda Abu
Aittomäki, Kristiina
Andrulis, Irene L
Anton-Culver, Hoda
Arndt, Volker
Aronson, Kristan J
Arun, Banu K
Auer, Paul L
Azzollini, Jacopo
Barrowdale, Daniel
Becher, Heiko
Beckmann, Matthias W
Behrens, Sabine
Benitez, Javier
Bermisheva, Marina
Bialkowska, Katarzyna
Blanco, Ana
Blomqvist, Carl
Bogdanova, Natalia V
Bojesen, Stig E
Bonanni, Bernardo
Bondavalli, Davide
Borg, Ake
Brauch, Hiltrud
Brenner, Hermann
Briceno, Ignacio
Broeks, Annegien
Brucker, Sara Y
Brüning, Thomas
Burwinkel, Barbara
Buys, Saundra S
Byers, Helen
Caldés, Trinidad
Caligo, Maria A
Calvello, Mariarosaria
Campa, Daniele
Castelao, Jose E
Chang-Claude, Jenny
Chanock, Stephen J
Christiaens, Melissa
Christiansen, Hans
Chung, Wendy K
Claes, Kathleen B M
Clarke, Christine L
Cornelissen, Sten
Couch, Fergus J
Cox, Angela
Cross, Simon S
Czene, Kamila
Daly, Mary B
Devilee, Peter
Diez, Orland
Domchek, Susan M
Dörk, Thilo
Dwek, Miriam
Eccles, Diana M
Ekici, Arif B
Evans, D Gareth
Fasching, Peter A
Figueroa, Jonine
Foretova, Lenka
Fostira, Florentia
Friedman, Eitan
Frost, Debra
Gago-Dominguez, Manuela
Gapstur, Susan M
Garber, Judy
García-Sáenz, José A
Gaudet, Mia M
Gayther, Simon A
Giles, Graham G
Godwin, Andrew K
Goldberg, Mark S
Goldgar, David E
González-Neira, Anna
Greene, Mark H
Gronwald, Jacek
Guénel, Pascal
Häberle, Lothar
Hahnen, Eric
Haiman, Christopher A
Hake, Christopher R
Hall, Per
Hamann, Ute
Harkness, Elaine F
Heemskerk-Gerritsen, Bernadette A M
Hillemanns, Peter
Hogervorst, Frans B L
Holleczek, Bernd
Hollestelle, Antoinette
Hooning, Maartje J
Hoover, Robert N
Hopper, John L
Howell, Anthony
Huebner, Hanna
Hulick, Peter J
Imyanitov, Evgeny N
Isaacs, Claudine
Izatt, Louise
Jager, Agnes
Jakimovska, Milena
Jakubowska, Anna
James, Paul
Janavicius, Ramunas
Janni, Wolfgang
John, Esther M
Jones, Michael E
Jung, Audrey
Kaaks, Rudolf
Kapoor, Pooja Middha
Karlan, Beth Y
Keeman, Renske
Khan, Sofia
Khusnutdinova, Elza
Kitahara, Cari M
Ko, Yon-Dschun
Konstantopoulou, Irene
Koppert, Linetta B
Koutros, Stella
Kristensen, Vessela N
Laenkholm, Anne-Vibeke
Lambrechts, Diether
Larsson, Susanna C
Laurent-Puig, Pierre
Lazaro, Conxi
Lazarova, Emilija
Lejbkowicz, Flavio
Leslie, Goska
Lesueur, Fabienne
Lindblom, Annika
Lissowska, Jolanta
Lo, Wing-Yee
Loud, Jennifer T
Lubinski, Jan
Lukomska, Alicja
MacInnis, Robert J
Mannermaa, Arto
Manoochehri, Mehdi
Manoukian, Siranoush
Margolin, Sara
Martinez, Maria Elena
Matricardi, Laura
McGuffog, Lesley
McLean, Catriona
Mebirouk, Noura
Meindl, Alfons
Menon, Usha
Miller, Austin
Mingazheva, Elvira
Montagna, Marco
Mulligan, Anna Marie
Mulot, Claire
Muranen, Taru A
Nathanson, Katherine L
Neuhausen, Susan L
Nevanlinna, Heli
Neven, Patrick
Newman, William G
Nielsen, Finn C
Nikitina-Zake, Liene
Nodora, Jesse
Offit, Kenneth
Olah, Edith
Olopade, Olufunmilayo I
Olsson, Håkan
Orr, Nick
Papi, Laura
Papp, Janos
Park-Simon, Tjoung-Won
Parsons, Michael T
Peissel, Bernard
Peixoto, Ana
Peshkin, Beth
Peterlongo, Paolo
Peto, Julian
Phillips, Kelly-Anne
Piedmonte, Marion
Plaseska-Karanfilska, Dijana
Prajzendanc, Karolina
Prentice, Ross
Prokofyeva, Darya
Rack, Brigitte
Radice, Paolo
Ramus, Susan J
Rantala, Johanna
Rashid, Muhammad U
Rennert, Gad
Rennert, Hedy S
Risch, Harvey A
Romero, Atocha
Rookus, Matti A
Rübner, Matthias
Rüdiger, Thomas
Saloustros, Emmanouil
Sampson, Sarah
Sandler, Dale P
Sawyer, Elinor J
Scheuner, Maren T
Schmutzler, Rita K
Schneeweiss, Andreas
Schoemaker, Minouk J
Schöttker, Ben
Schürmann, Peter
Senter, Leigha
Sharma, Priyanka
Sherman, Mark E
Shu, Xiao-Ou
Singer, Christian F
Smichkoska, Snezhana 
Soucy, Penny
Southey, Melissa C
Spinelli, John J
Stone, Jennifer
Stoppa-Lyonnet, Dominique
Swerdlow, Anthony J
Szabo, Csilla I
Tamimi, Rulla M
Tapper, William J
Taylor, Jack A
Teixeira, Manuel R
Terry, MaryBeth
Thomassen, Mads
Thull, Darcy L
Tischkowitz, Marc
Toland, Amanda E
Tollenaar, Rob A E M
Tomlinson, Ian
Torres, Diana
Troester, Melissa A
Truong, Thérèse
Tung, Nadine
Untch, Michael
Vachon, Celine M
van den Ouweland, Ans M W
van der Kolk, Lizet E
van Veen, Elke M
vanRensburg, Elizabeth J
Vega, Ana
Wappenschmidt, Barbara
Weinberg, Clarice R
Weitzel, Jeffrey N
Wildiers, Hans
Winqvist, Robert
Wolk, Alicja
Yang, Xiaohong R
Yannoukakos, Drakoulis
Zheng, Wei
Zorn, Kristin K
Milne, Roger L
Kraft, Peter
Simard, Jacques
Pharoah, Paul D P
Michailidou, Kyriaki
Antoniou, Antonis C
Schmidt, Marjanka K
Chenevix-Trench, Georgia
Easton, Douglas F
Chatterjee, Nilanjan
García-Closas, Montserrat
Issue Date: 2020
Publisher: Springer Science and Business Media LLC
Journal: Nature Genetics
Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
URI: http://hdl.handle.net/20.500.12188/8929
DOI: 10.1038/s41588-020-0609-2
Appears in Collections:Faculty of Medicine: Journal Articles

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