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Record W2918982382 · doi:10.1038/s41467-018-08053-5

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

2019· article· en· W2918982382 on OpenAlexaff
Manuel A. R. Ferreira, Eric R. Gamazon, Fares Al‐Ejeh, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton‐Culver, Aðalgeir Arason, Volker Arndt, Kristan J. Aronson, Banu Arun, Ella Asseryanis, Jacopo Azzollini, Judith Balmañà, Daniel R. Barnes, Daniel Barrowdale, Matthias W. Beckmann, Sabine Behrens, Javier Benı́tez, Marina Bermisheva, Katarzyna Białkowska, Carl Blomqvist, Natalia Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Åke Borg, Hiltrud Brauch, Hermann Brenner, Annegien Broeks, Barbara Burwinkel, Trinidad Caldés, Maria A. Caligo, Daniele Campa, Ian Campbell, Federico Canzian, Jonathan Carter, Brian D. Carter, Jose E. Castelao, Jenny Chang‐Claude, Stephen J. Chanock, Hans Christiansen, Wendy K. Chung, Kathleen Claes, Christine L. Clarke, Julian Adlard, Munaza Ahmed, Julian Barwell, Angela Brady, Carole Brewer, Jackie Cook, Rosemarie Davidson, Alan C. Donaldson, Jacqueline Eason, Ros Eeles, D. Gareth Evans, Helen Gregory, Helen Hanson, Alex Henderson, Shirley Hodgson, Louise Izatt, Michael J. Kennedy, Fiona Lalloo, Clare Miller, Patrick J. Morrison, Kai‐Ren Ong, Jo Perkins, Mary Porteous, Mark T. Rogers, Lucy Side, Katie Snape, Lisa Walker, Patricia A. Harrington, Norbert Arnold, Bernd Auber, Nadja Bogdanova-Markov, Julika Borde, Almuth Caliebe, Nina Ditsch, Bernd Dworniczak, Stefanie Engert, Ulrike Faust, Andrea Gehrig, Eric Hahnen, Jan Hauke, Julia Hentschel, Ellen Honisch, Walter Just, Karin Kast, Mirjam Larsen, Johannes Lemke, Huu Phuc Nguyen, Dieter Niederacher, Claus‐Eric Ott, Konrad Platzer, Esther Pohl‐Rescigno, Juliane Ramser, Kerstin Rhiem, Doris Steinemann, Christian Sutter, Raymonda Varon-Mateeva, Shan Wang‐Gohrke, Bernhard H. F. Weber, Fabienne Prieur, Pascal Pujol, Charlotte Sagne, Nicolas Sévenet, Hagay Sobol, Johanna Sokolowska, Dominique Stoppa-Lyonnet, Laurence Venat-Bouvet, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Miguel de la Hoya, Joe Dennis, Peter Devilee, Orland Dı́ez, Thilo Dörk, Alison M. Dunning, Miriam Dwek, Bent Ejlertsen, Carolina Ellberg, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Eitan Friedman, Debra Frost, Marike Gabrielson, Manuela Gago-Domínguez, Patricia A. Ganz, Susan M. Gapstur, Judy E. Garber, Montserrat García‐Closas, José Á. García-Sáenz, Mia M. Gaudet, Graham G. Giles, Gord Glendon, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González‐Neira, Mark H. Greene, Jacek Gronwald, Pascal Guénel, Christopher A. Haiman, Per Hall, U. Hamann, Wei He, Jane Heyworth, Antoinette Hollestelle, Robert N. Hoover, John L. Hopper, Peter J. Hulick, Keith Humphreys, Evgeny N. Imyanitov, Rosemary L. Balleine, Robert Baxter, Stephen Braye, Jane Carpenter, Jane E. Dahlstrom, John Forbes, Deborah J. Marsh, Adrienne Morey, Nirmala Pathmanathan, Peter Simpson, Allan D. Spigelman, Nicholas Wilcken, Desmond Yip, Bernadette A. M. Heemskerk‐Gerritsen, Matti A. Rookus, Caroline Seynaeve, Frederieke H. van der Baan, Annemieke H. van der Hout, Lizet E. van der Kolk, Rob B. van der Luijt, Carolien H. M. van Deurzen, Helena C. van Doorn, Klaartje van Engelen, Liselotte van Hest, Theo A.M. van Os, Senno Verhoef, Maartje J. Vogel, Juul Wijnen, Alexander Miron, Miroslav Kapuscinski, Anita Bane, Eric A. Ross, Saundra S. Buys, Thomas Conner, Claudine Isaacs, Milena Jakimovska, Anna Jakubowska, Paul A. James, Ramunas Janavicius, Rachel C. Jankowitz, Esther M. John, Nichola Johnson, Joseph Vijai, Beth Y. Karlan, Э. К. Хуснутдинова, Johanna I. Kiiski, Yon‐Dschun Ko, Michael E. Jones, Irene Konstantopoulou, Vessela N. Kristensen, Yael Laitman, Diether Lambrechts, Conxi Lázaro, Goska Leslie, Jenny Lester, Fabienne Lesueur, Sara Lindström, Jirong Long, Jennifer T. Loud, Jan Lubiński, Enes Makalic, Mehdi Manoochehri, Sara Margolin, Tabea Maurer, Dimitrios Mavroudis, Lesley McGuffog, Alfons Meindl, Usha Menon, Kyriaki Michailidou, Austin Miller, Marco Montagna, Fernando Moreno, Lidia Moserle, Anna Marie Mulligan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Ines Nevelsteen, Finn C. Nielsen, Liene Ņikitina-Zaķe, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Håkan Olsson, Ana Osório, J. Papp, Tjoung-Won Park-Simon, Michael T. Parsons, Inge Søkilde Pedersen, Ana Peixoto, Paolo Peterlongo, Paul D.P. Pharoah, Dijana Plaseska-Karanfilska, Bruce Poppe, Nadège Presneau, Paolo Radice, Johanna Rantala, Gad Rennert, Harvey A. Risch, Emmanouil Saloustros, Kristin Sanden, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Priyanka Sharma, Xiao-Ou Shu, Jacques Simard, Christian F. Singer, Penny Soucy, Melissa C. Southey, John J. Spinelli, Amanda B. Spurdle, Jennifer Stone, Anthony J. Swerdlow, William Tapper, Jack A. Taylor, Manuel R. Teixeira, Mary Beth Terry, Àlex Teulé, Mads Thomassen, Kathrin Thöne, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Thérèse Truong, Nadine Tung, Celine M. Vachon, Christi J. van Asperen, Ans M.W. van den Ouweland, Elizabeth J. van Rensburg, Ana Vega, Alessandra Viel, Qin Wang, Barbara Wappenschmidt, Jeffrey N. Weitzel, Camilla Wendt, Robert Winqvist, Xiaohong R. Yang, Drakoulis Yannoukakos, Argyrios Ziogas, Peter Kraft, Antonis C. Antoniou, Wei Zheng, Douglas F. Easton, Roger L. Milne, Georgia Chenevix‐Trench

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Chromatin Dynamics
Canadian institutionsUniversity of British ColumbiaUniversité LavalRoyal Victoria HospitalCentre hospitalier universitaire de QuébecMcGill UniversityUniversity Health NetworkUniversity of TorontoMcMaster UniversityJuravinski HospitalQueen's UniversityLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersNational Center for Advancing Translational SciencesNational Cancer InstituteMedical Research CouncilNational Institute for Health and Care ResearchCancer Research UK
KeywordsTranscriptomeBreast cancerGenome-wide association studyGeneComputational biologyGeneticsGenomeBiologyCancerBioinformaticsSingle-nucleotide polymorphismGene expressionGenotype

Abstract

fetched live from OpenAlex

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.167
Threshold uncertainty score0.378

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.286
Teacher spread0.277 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations138
Published2019
Admission routes1
Has abstractyes

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