Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element
dc.date.accessioned | 2022-04-05T18:44:30Z | |
dc.date.available | 2022-04-05T18:44:30Z | |
dc.date.created | 2022-02-23T19:40:53Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Baxter, Joseph S. Johnson, Nichola Tomczyk, Katarzyna Gillespie, Andrea Maguire, Sarah Brough, Rachel Fachal, Laura Michailidou, Kyriaki Bolla, Manjeet K. Wang, Qin Dennis, Joe Ahearn, Thomas U. Andrulis, Irene L. Anton-Culver, Hoda Antonenkova, Natalia N Arndt, Volker Aronson, Kristian J. Augustinsson, Annelie Becher, Heiko Beckmann, Matthias W. Behrens, Sabine Benitez, Javier Bermisheva, Marina Bogdanova, Natalia V. Bojesen, Stig E. Brenner, Hermann Brucker, Sara Y. Cai, Qiuyin Campa, Daniele Canzian, Federico Castelao, Jose E. Chan, Tsun L. Chang-Claude, Jenny Chanock, Stephen J. Chenevix-Trench, Georgia Choi, Ji-Yeob Clarke, Christine L. Colonna, Sarah Conroy, Don M. Couch, Fergus J. Cox, Angela Cross, Simon S. Czene, Kamila Daly, Mary B. Devilee, Peter Dörk, Thilo Dossus, Laure Dwek, Miriam Eccles, Diana M. Ekici, Arif B. Eliassen, A. Heather Engel, Christoph Fasching, Peter A. Figueroa, Jonine Flyger, Henrik Gago-Dominguez, Manuela Gao, Chi García-Closas, Montserrat García-Sáenz, José A. Ghoussaini, Maya Giles, Graham G. Goldberg, Mark S. González-Neira, Anna Guénel, Pascal Gündert, Melanie Haeberle, Lothar Hahnen, Eric Haiman, Christopher A. Hall, Per Hamann, Ute Hartman, Mikael Hatse, Sigrid Hauke, Jan Hollestelle, Antoinette Hoppe, Reiner Hopper, John L. Hou, Ming-Feng Ito, Hidemi Iwasaki, Motoki Jager, Agnes Jakubowska, Anna Janni, Wolfgang John, Esther M. Joseph, Vijai Jung, Audrey Kaaks, Rudolf Kang, Daehee Keeman, Renske Khusnutdinova, Elza Kim, Sung-Won Kosma, Veli-Matti Kraft, Peter Kristensen, Vessela N. Kubelka-Sabit, Katerina Kurian, Allison W. Kwong, Ava Lacey, James V. Lambrechts, Diether Larson, Nicole L. Larsson, Susanna C. Le Marchand, Loic Lejbkowicz, F Li, Jingmei Long, Jirong Lophatananon, Artitaya Lubinski, Jan Mannermaa, Arto Manoochehri, Mehdi Manoukian, Siranoush Margolin, Sara Matsuo, Keitaro Mavroudis, Dimitrios Mayes, Rebecca Menon, Usha Milne, Roger L. Mohd Taib, Nur Aishah Muir, Kenneth Muranen, TA Murphy, Rachel A. Nevanlinna, Heli O'Brien, Katie M. Offit, Kenneth Olson, Janet E. Olsson, Håkan Park, Sue K. Park-Simon, Tjoung-Won Patel, Alpa V. Peterlongo, Paolo Peto, Julian Plaseska-Karanfilska, Dijana Presneau, Nadege Pylkäs, Katri Rack, Brigitte Rennert, Gad Romero, Atocha Ruebner, Matthias Rüdiger, Thomas Saloustros, Emmanouil Sandler, Dale P. Sawyer, Elinor J. Schmidt, Marjanka K. Schmutzler, Rita K. Schneeweiss, Andreas Schoemaker, Minouk J. Shah, Mitul Shen, Chen-Yang Shu, Xiao-Ou Simard, Jacques Southey, Melissa C. Stone, Jennifer Surowy, Harald Swerdlow, Anthony Tamimi, Rulla M. Tapper, William J. Taylor, Jack A. Teo, Soo Hwang Teras, Lauren R. Terry, Mary Beth Toland, Amanda E. Tomlinson, Ian Truong, Thérèse Tseng, Chiu-Chen Untch, Michael Vachon, Celine van den Ouweland, Ans M.W. Wang, Sophia S. Weinberg, Clarice R. Wendt, Camilla Winham, Stacey J. Winqvist, Robert Wolk, Alicja Wu, Annah H. Yamaji, Taiki Zheng, Wei Ziogas, Argyrios Pharoah, Paul D.P. Dunning, Alison M. Easton, Douglas F. Pettitt, Stephen J. Lord, Christopher J. Haider, Syed Orr, Nick Fletcher, Olivia . Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element. American Journal of Human Genetics. 2021, 108(7), 1190-1203 | |
dc.identifier.uri | http://hdl.handle.net/10852/93336 | |
dc.description.abstract | A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74–0.81, p = 3.1 × 10−31). | |
dc.language | EN | |
dc.publisher | University of Chicago Press | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element | |
dc.type | Journal article | |
dc.creator.author | Baxter, Joseph S. | |
dc.creator.author | Johnson, Nichola | |
dc.creator.author | Tomczyk, Katarzyna | |
dc.creator.author | Gillespie, Andrea | |
dc.creator.author | Maguire, Sarah | |
dc.creator.author | Brough, Rachel | |
dc.creator.author | Fachal, Laura | |
dc.creator.author | Michailidou, Kyriaki | |
dc.creator.author | Bolla, Manjeet K. | |
dc.creator.author | Wang, Qin | |
dc.creator.author | Dennis, Joe | |
dc.creator.author | Ahearn, Thomas U. | |
dc.creator.author | Andrulis, Irene L. | |
dc.creator.author | Anton-Culver, Hoda | |
dc.creator.author | Antonenkova, Natalia N | |
dc.creator.author | Arndt, Volker | |
dc.creator.author | Aronson, Kristian J. | |
dc.creator.author | Augustinsson, Annelie | |
dc.creator.author | Becher, Heiko | |
dc.creator.author | Beckmann, Matthias W. | |
dc.creator.author | Behrens, Sabine | |
dc.creator.author | Benitez, Javier | |
dc.creator.author | Bermisheva, Marina | |
dc.creator.author | Bogdanova, Natalia V. | |
dc.creator.author | Bojesen, Stig E. | |
dc.creator.author | Brenner, Hermann | |
dc.creator.author | Brucker, Sara Y. | |
dc.creator.author | Cai, Qiuyin | |
dc.creator.author | Campa, Daniele | |
dc.creator.author | Canzian, Federico | |
dc.creator.author | Castelao, Jose E. | |
dc.creator.author | Chan, Tsun L. | |
dc.creator.author | Chang-Claude, Jenny | |
dc.creator.author | Chanock, Stephen J. | |
dc.creator.author | Chenevix-Trench, Georgia | |
dc.creator.author | Choi, Ji-Yeob | |
dc.creator.author | Clarke, Christine L. | |
dc.creator.author | Colonna, Sarah | |
dc.creator.author | Conroy, Don M. | |
dc.creator.author | Couch, Fergus J. | |
dc.creator.author | Cox, Angela | |
dc.creator.author | Cross, Simon S. | |
dc.creator.author | Czene, Kamila | |
dc.creator.author | Daly, Mary B. | |
dc.creator.author | Devilee, Peter | |
dc.creator.author | Dörk, Thilo | |
dc.creator.author | Dossus, Laure | |
dc.creator.author | Dwek, Miriam | |
dc.creator.author | Eccles, Diana M. | |
dc.creator.author | Ekici, Arif B. | |
dc.creator.author | Eliassen, A. Heather | |
dc.creator.author | Engel, Christoph | |
dc.creator.author | Fasching, Peter A. | |
dc.creator.author | Figueroa, Jonine | |
dc.creator.author | Flyger, Henrik | |
dc.creator.author | Gago-Dominguez, Manuela | |
dc.creator.author | Gao, Chi | |
dc.creator.author | García-Closas, Montserrat | |
dc.creator.author | García-Sáenz, José A. | |
dc.creator.author | Ghoussaini, Maya | |
dc.creator.author | Giles, Graham G. | |
dc.creator.author | Goldberg, Mark S. | |
dc.creator.author | González-Neira, Anna | |
dc.creator.author | Guénel, Pascal | |
dc.creator.author | Gündert, Melanie | |
dc.creator.author | Haeberle, Lothar | |
dc.creator.author | Hahnen, Eric | |
dc.creator.author | Haiman, Christopher A. | |
dc.creator.author | Hall, Per | |
dc.creator.author | Hamann, Ute | |
dc.creator.author | Hartman, Mikael | |
dc.creator.author | Hatse, Sigrid | |
dc.creator.author | Hauke, Jan | |
dc.creator.author | Hollestelle, Antoinette | |
dc.creator.author | Hoppe, Reiner | |
dc.creator.author | Hopper, John L. | |
dc.creator.author | Hou, Ming-Feng | |
dc.creator.author | Ito, Hidemi | |
dc.creator.author | Iwasaki, Motoki | |
dc.creator.author | Jager, Agnes | |
dc.creator.author | Jakubowska, Anna | |
dc.creator.author | Janni, Wolfgang | |
dc.creator.author | John, Esther M. | |
dc.creator.author | Joseph, Vijai | |
dc.creator.author | Jung, Audrey | |
dc.creator.author | Kaaks, Rudolf | |
dc.creator.author | Kang, Daehee | |
dc.creator.author | Keeman, Renske | |
dc.creator.author | Khusnutdinova, Elza | |
dc.creator.author | Kim, Sung-Won | |
dc.creator.author | Kosma, Veli-Matti | |
dc.creator.author | Kraft, Peter | |
dc.creator.author | Kristensen, Vessela N. | |
dc.creator.author | Kubelka-Sabit, Katerina | |
dc.creator.author | Kurian, Allison W. | |
dc.creator.author | Kwong, Ava | |
dc.creator.author | Lacey, James V. | |
dc.creator.author | Lambrechts, Diether | |
dc.creator.author | Larson, Nicole L. | |
dc.creator.author | Larsson, Susanna C. | |
dc.creator.author | Le Marchand, Loic | |
dc.creator.author | Lejbkowicz, F | |
dc.creator.author | Li, Jingmei | |
dc.creator.author | Long, Jirong | |
dc.creator.author | Lophatananon, Artitaya | |
dc.creator.author | Lubinski, Jan | |
dc.creator.author | Mannermaa, Arto | |
dc.creator.author | Manoochehri, Mehdi | |
dc.creator.author | Manoukian, Siranoush | |
dc.creator.author | Margolin, Sara | |
dc.creator.author | Matsuo, Keitaro | |
dc.creator.author | Mavroudis, Dimitrios | |
dc.creator.author | Mayes, Rebecca | |
dc.creator.author | Menon, Usha | |
dc.creator.author | Milne, Roger L. | |
dc.creator.author | Mohd Taib, Nur Aishah | |
dc.creator.author | Muir, Kenneth | |
dc.creator.author | Muranen, TA | |
dc.creator.author | Murphy, Rachel A. | |
dc.creator.author | Nevanlinna, Heli | |
dc.creator.author | O'Brien, Katie M. | |
dc.creator.author | Offit, Kenneth | |
dc.creator.author | Olson, Janet E. | |
dc.creator.author | Olsson, Håkan | |
dc.creator.author | Park, Sue K. | |
dc.creator.author | Park-Simon, Tjoung-Won | |
dc.creator.author | Patel, Alpa V. | |
dc.creator.author | Peterlongo, Paolo | |
dc.creator.author | Peto, Julian | |
dc.creator.author | Plaseska-Karanfilska, Dijana | |
dc.creator.author | Presneau, Nadege | |
dc.creator.author | Pylkäs, Katri | |
dc.creator.author | Rack, Brigitte | |
dc.creator.author | Rennert, Gad | |
dc.creator.author | Romero, Atocha | |
dc.creator.author | Ruebner, Matthias | |
dc.creator.author | Rüdiger, Thomas | |
dc.creator.author | Saloustros, Emmanouil | |
dc.creator.author | Sandler, Dale P. | |
dc.creator.author | Sawyer, Elinor J. | |
dc.creator.author | Schmidt, Marjanka K. | |
dc.creator.author | Schmutzler, Rita K. | |
dc.creator.author | Schneeweiss, Andreas | |
dc.creator.author | Schoemaker, Minouk J. | |
dc.creator.author | Shah, Mitul | |
dc.creator.author | Shen, Chen-Yang | |
dc.creator.author | Shu, Xiao-Ou | |
dc.creator.author | Simard, Jacques | |
dc.creator.author | Southey, Melissa C. | |
dc.creator.author | Stone, Jennifer | |
dc.creator.author | Surowy, Harald | |
dc.creator.author | Swerdlow, Anthony | |
dc.creator.author | Tamimi, Rulla M. | |
dc.creator.author | Tapper, William J. | |
dc.creator.author | Taylor, Jack A. | |
dc.creator.author | Teo, Soo Hwang | |
dc.creator.author | Teras, Lauren R. | |
dc.creator.author | Terry, Mary Beth | |
dc.creator.author | Toland, Amanda E. | |
dc.creator.author | Tomlinson, Ian | |
dc.creator.author | Truong, Thérèse | |
dc.creator.author | Tseng, Chiu-Chen | |
dc.creator.author | Untch, Michael | |
dc.creator.author | Vachon, Celine | |
dc.creator.author | van den Ouweland, Ans M.W. | |
dc.creator.author | Wang, Sophia S. | |
dc.creator.author | Weinberg, Clarice R. | |
dc.creator.author | Wendt, Camilla | |
dc.creator.author | Winham, Stacey J. | |
dc.creator.author | Winqvist, Robert | |
dc.creator.author | Wolk, Alicja | |
dc.creator.author | Wu, Annah H. | |
dc.creator.author | Yamaji, Taiki | |
dc.creator.author | Zheng, Wei | |
dc.creator.author | Ziogas, Argyrios | |
dc.creator.author | Pharoah, Paul D.P. | |
dc.creator.author | Dunning, Alison M. | |
dc.creator.author | Easton, Douglas F. | |
dc.creator.author | Pettitt, Stephen J. | |
dc.creator.author | Lord, Christopher J. | |
dc.creator.author | Haider, Syed | |
dc.creator.author | Orr, Nick | |
dc.creator.author | Fletcher, Olivia | |
cristin.unitcode | 185,53,18,10 | |
cristin.unitname | Avdeling for medisinsk genetikk | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 2004980 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=American Journal of Human Genetics&rft.volume=108&rft.spage=1190&rft.date=2021 | |
dc.identifier.jtitle | American Journal of Human Genetics | |
dc.identifier.volume | 108 | |
dc.identifier.issue | 7 | |
dc.identifier.startpage | 1190 | |
dc.identifier.endpage | 1203 | |
dc.identifier.doi | https://doi.org/10.1016/j.ajhg.2021.05.013 | |
dc.identifier.urn | URN:NBN:no-95931 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0002-9297 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/93336/1/1-s2.0-S0002929721002184-main.pdf | |
dc.type.version | PublishedVersion |
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