Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2
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Author
Orr, Nick
Dudbridge, Frank
Dryden, Nicola
Maguire, Sarah
Novo, Daniela
Perrakis, Eleni
Johnson, Nichola
Ghoussaini, Maya
Hopper, John L.
Southey, Melissa C.
Apicella, Carmel
Stone, Jennifer
Schmidt, Marjanka K.
Broeks, Annegien
Van't Veer, Laura J.
Hogervorst, Frans B.
Fasching, Peter A.
Haeberle, Lothar
Ekici, Arif B.
Beckmann, Matthias W.
Gibson, Lorna
Aitken, Zoe
Warren, Helen
Sawyer, Elinor
Tomlinson, Ian
Kerin, Michael J.
Miller, Nicola
Burwinkel, Barbara
Marme, Frederik
Schneeweiss, Andreas
Sohn, Chistof
Guénel, Pascal
Truong, Thérèse
Cordina-Duverger, Emilie
Sanchez, Marie
Bojesen, Stig E.
Nordestgaard, Børge G.
Nielsen, Sune F.
Flyger, Henrik
Benitez, Javier
Zamora, Maria Pilar
Arias Perez, Jose Ignacio
Menéndez, Primitiva
Anton-Culver, Hoda
Neuhausen, Susan L.
Brenner, Hermann
Dieffenbach, Aida Karina
Arndt, Volker
Stegmaier, Christa
Hamann, Ute
Brauch, Hiltrud
Justenhoven, Christina
Brüning, Thomas
Ko, Yon-Dschun
Nevanlinna, Heli
Aittomäki, Kristiina
Blomqvist, Carl
Khan, Sofia
Bogdanova, Natalia
Dörk, Thilo
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Chenevix-Trench, Georgia
Beesley, Jonathan
Lambrechts, Diether
Moisse, Matthieu
Floris, Guiseppe
Beuselinck, Benoit
Chang-Claude, Jenny
Rudolph, Anja
Seibold, Petra
Flesch-Janys, Dieter
Radice, Paolo
Peterlongo, Paolo
Peissel, Bernard
Pensotti, Valeria
Couch, Fergus J.
Olson, Janet E.
Slettedahl, Seth
Vachon, Celine
Giles, Graham G.
Milne, Roger L.
McLean, Catriona
Haiman, Christopher A.
Henderson, Brian E.
Schumacher, Fredrick
Le Marchand, Loic
Simard, Jacques
Goldberg, Mark S.
Labrèche, France
Dumont, Martine
Kristensen, Vessela
Alnæs, Grethe Grenaker
Nord, Silje
Borresen-Dale, Anne-Lise
Zheng, Wei
Deming-Halverson, Sandra
Shrubsole, Martha
Long, Jirong
Winqvist, Robert
Pylkäs, Katri
Jukkola-Vuorinen, Arja
Grip, Mervi
Andrulis, Irene L.
Knight, Julia A.
Glendon, Gord
Tchatchou, Sandrine
Devilee, Peter
Tollenaar, Robertus A. E. M.
Seynaeve, Caroline M.
Van Asperen, Christi J.
Garcia-Closas, Montserrat
Figueroa, Jonine
Chanock, Stephen J.
Lissowska, Jolanta
Czene, Kamila
Darabi, Hatef
Eriksson, Mikael
Klevebring, Daniel
Hooning, Maartje J.
Hollestelle, Antoinette
van Deurzen, Carolien H. M.
Kriege, Mieke
Hall, Per
Li, Jingmei
Liu, Jianjun
Humphreys, Keith
Cox, Angela
Cross, Simon S.
Reed, Malcolm W. R.
Pharoah, Paul D. P.
Dunning, Alison M.
Shah, Mitul
Perkins, Barbara J.
Jakubowska, Anna
Lubinski, Jan
Jaworska-Bieniek, Katarzyna
Durda, Katarzyna
Ashworth, Alan
Swerdlow, Anthony
Jones, Michael
Schoemaker, Minouk J.
Meindl, Alfons
Schmutzler, Rita K.
Olswold, Curtis
Slager, Susan
Toland, Amanda E.
Yannoukakos, Drakoulis
Muir, Kenneth
Lophatananon, Artitaya
Stewart-Brown, Sarah
Siriwanarangsan, Pornthep
Matsuo, Keitaro
Ito, Hidema
Iwata, Hiroji
Ishiguro, Junko
Wu, Anna H.
Tseng, Chiu-chen
Van Den Berg, David
Stram, Daniel O.
Teo, Soo Hwang
Yip, Cheng Har
Kang, Peter
Ikram, Mohammad Kamran
Shu, Xiao-Ou
Lu, Wei
Gao, Yu-Tang
Cai, Hui
Kang, Daehee
Choi, Ji-Yeob
Park, Sue K.
Noh, Dong-Young
Hartman, Mikael
Miao, Hui
Lim, Wei Yen
Lee, Soo Chin
Sangrajrang, Suleeporn
Gaborieau, Valerie
Brennan, Paul
Mckay, James
Wu, Pei-Ei
Hou, Ming-Feng
Yu, Jyh-Cherng
Shen, Chen-Yang
Blot, William
Cai, Qiuyin
Luccarini, Craig
Bayes, Caroline
Ahmed, Shahana
Maranian, Mel
Healey, Catherine S.
González-Neira, Anna
Pita, Guillermo
Alonso, M. Rosario
Álvarez, Nuria
Herrero, Daniel
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francois
Lindstrom, Sara
Dennis, Joe
Michailidou, Kyriaki
Bolla, Manjeet K.
Easton, Douglas F.
dos Santos Silva, Isabel
Fletcher, Olivia
Peto, Julian
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1093/hmg/ddv035Metadata
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Orr, N., F. Dudbridge, N. Dryden, S. Maguire, D. Novo, E. Perrakis, N. Johnson, et al. 2015. “Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2.” Human Molecular Genetics 24 (10): 2966-2984. doi:10.1093/hmg/ddv035. http://dx.doi.org/10.1093/hmg/ddv035.Abstract
We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88–0.92]; P-value = 1.58 × 10−25). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08–1.17]; P-value = 7.89 × 10−09) and rs13294895 (OR = 1.09 [1.06–1.12]; P-value = 2.97 × 10−11). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06–1.18]; P-value = 2.77 × 10−05). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406292/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:15034800
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Van Tyne, Daria Natalie; Park, Daniel John; Schaffner, Stephen; Neafsey, Daniel Edward; Angelino, Elaine Lee; Cortese, Joseph F.; Barnes, Kayla G.; Rosen, David M.; Lukens, Amanda Kathleen; Daniels, Rachel Fath; Milner, Danny Arnold; Johnson, Charles A.; Shlyakhter, Ilya; Grossman, Sharon Rachel; Becker, Justin S.; Yamins, Daniel Louis Kanef; Karlsson, Elinor Kathryn; Ndiaye, Daouda; Sarr, Ousmane; Mboup, Souleymane; Happi, Christian Tientcha; Furlotte, Nicholas A.; Eskin, Eleazar; Kang, Hyun Min; Hartl, Daniel L.; Birren, Bruce W.; Wiegand, Roger C.; Lander, Eric Steven; Wirth, Dyann Fergus; Cooke, Sarah Volkman; Sabeti, Pardis Christine (Public Library of Science, 2011)The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis ... -
The Third Data Release of the Sloan Digital Sky Survey
Abazajian, Kevork; Adelman-McCarthy, Jennifer K.; Agüeros, Marcel A.; Allam, Sahar S.; Anderson, Kurt S. J.; Anderson, Scott F.; Annis, James; Bahcall, Neta A.; Baldry, Ivan K.; Bastian, Steven; Berlind, Andreas; Bernardi, Mariangela; Blanton, Michael R.; Bochanski, John J. Jr.; Boroski, William N.; Brewington, Howard J.; Briggs, John W.; Brinkmann, J.; Brunner, Robert J.; Budavári, Tamás; Carey, Larry N.; Castander, Francisco J.; Connolly, A. J.; Covey, Kevin R.; Csabai, István; Dalcanton, Julianne J.; Doi, Mamoru; Dong, Feng; Eisenstein, Daniel James; Evans, Michael L.; Fan, Xiaohui; Finkbeiner, Douglas; Friedman, Scott D.; Frieman, Joshua A.; Fukugita, Masataka; Gillespie, Bruce; Glazebrook, Karl; Gray, Jim; Grebel, Eva K.; Gunn, James E.; Gurbani, Vijay K.; Hall, Patrick B.; Hamabe, Masaru; Harbeck, Daniel; Harris, Frederick H.; Harris, Hugh C.; Harvanek, Michael; Hawley, Suzanne L.; Hayes, Jeffrey; Heckman, Timothy M.; Hendry, John S.; Hennessy, Gregory S.; Hindsley, Robert B.; Hogan, Craig J.; Hogg, David W.; Holmgren, Donald J.; Holtzman, Jon A.; Ichikawa, Shin-ichi; Ichikawa, Takashi; Ivezic, Zeljko; Jester, Sebastian; Johnston, David E.; Jorgensen, Anders M.; Juri?, Mario; Kent, Stephen M.; Kleinman, S. J.; Knapp, G. R.; Kniazev, Alexei Yu.; Kron, Richard G.; Krzesinski, Jurek; Lamb, Donald Q.; Lampeitl, Hubert; Lee, Brian C.; Lin, Huan; Long, Daniel C.; Loveday, Jon; Lupton, Robert H.; Mannery, Ed; Margon, Bruce; Martínez-Delgado, David; Matsubara, Takahiko; McGehee, Peregrine M.; McKay, Timothy A.; Meiksin, Avery; Ménard, Brice; Munn, Jeffrey A.; Nash, Thomas; Neilsen, Eric H. Jr.; Newberg, Heidi Jo; Newman, Peter R.; Nichol, Robert C.; Nicinski, Tom; Nieto-Santisteban, Maria; Nitta, Atsuko; Okamura, Sadanori; O, William; Owen, Russell; Padmanabhan, Nikhil; Pauls, George; Peoples, John; Pier, Jeffrey R.; Pope, Adrian C.; Pourbaix, Dimitri; Quinn, Thomas R.; Raddick, M. Jordan; Richards, Gordon T.; Richmond, Michael W.; Rix, Hans-Walter; Rockosi, Constance M.; Schlegel, David J.; Schneider, Donald P.; Schroeder, Joshua; Scranton, Ryan; Sekiguchi, Maki; Sheldon, Erin; Shimasaku, Kazu; Silvestri, Nicole M.; Smith, J. Allyn; Smol?i?, Vernesa; Snedden, Stephanie A.; Stebbins, Albert; Stoughton, Chris; Strauss, Michael A.; SubbaRao, Mark; Szalay, Alexander S.; Szapudi, István; Szkody, Paula; Szokoly, Gyula P.; Tegmark, Max; Teodoro, Luis; Thakar, Aniruddha R.; Tremonti, Christy; Tucker, Douglas L.; Uomoto, Alan; Vanden Berk, Daniel E.; Vandenberg, Jan; Vogeley, Michael S.; Voges, Wolfgang; Vogt, Nicole P.; Walkowicz, Lucianne M.; Wang, Shu-i; Weinberg, David H.; West, Andrew A.; White, Simon D. M.; Wilhite, Brian C.; Xu, Yongzhong; Yanny, Brian; Yasuda, Naoki; Yip, Ching-Wa; Yocum, D. R.; York, Donald G.; Zehavi, Idit; Zibetti, Stefano; Zucker, Daniel B. (IOP Publishing, 2005)This paper describes the Third Data Release of the Sloan Digital Sky Survey (SDSS). This release, containing data taken up through 2003 June, includes imaging data in five bands over 5282 deg2, photometric and astrometric ...