Transcriptome-wide association study of breast cancer risk by estrogen-receptor status: Genetic Epidemiology

H. Feng, A. Gusev, B. Pasaniuc, L. Wu, J. Long, Z. Abu-full, K. Aittomäki, I.L. Andrulis, H. Anton-Culver, A.C. Antoniou, A. Arason, V. Arndt, K.J. Aronson, B.K. Arun, E. Asseryanis, P.L. Auer, J. Azzollini, J. Balmaña, R.B. Barkardottir, D.R. BarnesD. Barrowdale, M.W. Beckmann, S. Behrens, J. Benitez, M. Bermisheva, K. Białkowska, A. Blanco, C. Blomqvist, B. Boeckx, N.V. Bogdanova, S.E. Bojesen, M.K. Bolla, B. Bonanni, A. Borg, H. Brauch, H. Brenner, I. Briceno, A. Broeks, T. Brüning, B. Burwinkel, Q. Cai, T. Caldés, M.A. Caligo, I. Campbell, S. Canisius, D. Campa, B.D. Carter, J. Carter, J.E. Castelao, J. Chang-Claude, S.J. Chanock, H. Christiansen, W.K. Chung, K.B.M. Claes, C.L. Clarke, F.J. Couch, A. Cox, S.S. Cross, C. Cybulski, K. Czene, M.B. Daly, M. de la Hoya, K. De Leeneer, J. Dennis, P. Devilee, O. Diez, S.M. Domchek, T. Dörk, I. dos-Santos-Silva, A.M. Dunning, M. Dwek, D.M. Eccles, B. Ejlertsen, C. Ellberg, C. Engel, M. Eriksson, P.A. Fasching, O. Fletcher, H. Flyger, F. Fostira, E. Friedman, L. Fritschi, D. Frost, M. Gabrielson, P.A. Ganz, S.M. Gapstur, J. Garber, M. García-Closas, J.A. García-Sáenz, M.M. Gaudet, G.G. Giles, G. Glendon, A.K. Godwin, M.S. Goldberg, D.E. Goldgar, A. González-Neira, M.H. Greene, J. Gronwald, P. Guénel, C.A. Haiman, P. Hall, U. Hamann, C. Hake, W. He, J. Heyworth, F.B.L. Hogervorst, A. Hollestelle, M.J. Hooning, R.N. Hoover, J.L. Hopper, G. Huang, P.J. Hulick, K. Humphreys, E.N. Imyanitov, C. Isaacs, M. Jakimovska, A. Jakubowska, P. James, R. Janavicius, R.C. Jankowitz, E.M. John, N. Johnson, V. Joseph, A. Jung, B.Y. Karlan, E. Khusnutdinova, J.I. Kiiski, I. Konstantopoulou, V.N. Kristensen, Y. Laitman, D. Lambrechts, C. Lazaro, D. Leroux, G. Leslie, J. Lester, F. Lesueur, N. Lindor, S. Lindström, W.-Y. Lo, J.T. Loud, J. Lubiński, E. Makalic, A. Mannermaa, M. Manoochehri, S. Manoukian, S. Margolin, J.W.M. Martens, M.E. Martinez, L. Matricardi, T. Maurer, D. Mavroudis, L. McGuffog, A. Meindl, U. Menon, K. Michailidou, P.M. Kapoor, A. Miller, M. Montagna, F. Moreno, L. Moserle, A.M. Mulligan, T.A. Muranen, K.L. Nathanson, S.L. Neuhausen, H. Nevanlinna, I. Nevelsteen, F.C. Nielsen, L. Nikitina-Zake, K. Offit, E. Olah, O.I. Olopade, H. Olsson, A. Osorio, J. Papp, T.-W. Park-Simon, M.T. Parsons, I.S. Pedersen, A. Peixoto, P. Peterlongo, J. Peto, P.D.P. Pharoah, K.-A. Phillips, D. Plaseska-Karanfilska, B. Poppe, N. Pradhan, K. Prajzendanc, N. Presneau, K. Punie, K. Pylkäs, P. Radice, J. Rantala, M.U. Rashid, G. Rennert, H.A. Risch, M. Robson, A. Romero, E. Saloustros, D.P. Sandler, C. Santos, E.J. Sawyer, M.K. Schmidt, D.F. Schmidt, R.K. Schmutzler, M.J. Schoemaker, R.J. Scott, P. Sharma, X.-O. Shu, J. Simard, C.F. Singer, A.-B. Skytte, P. Soucy, M.C. Southey, J.J. Spinelli, A.B. Spurdle, J. Stone, A.J. Swerdlow, W.J. Tapper, J.A. Taylor, M.R. Teixeira, M.B. Terry, A. Teulé, M. Thomassen, K. Thöne, D.L. Thull, M. Tischkowitz, A.E. Toland, R.A.E.M. Tollenaar, D. Torres, T. Truong, N. Tung, C.M. Vachon, C.J. van Asperen, A.M.W. van den Ouweland, E.J. van Rensburg, A. Vega, A. Viel, P. Vieiro-Balo, Q. Wang, B. Wappenschmidt, C.R. Weinberg, J.N. Weitzel, C. Wendt, R. Winqvist, X.R. Yang, D. Yannoukakos, A. Ziogas, R.L. Milne, D.F. Easton, G. Chenevix-Trench, W. Zheng, P. Kraft, X. Jiang, GEMO Study Collaborators, EMBRACE Collaborators, GC-HBOC study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators, OCGN Investigators

Research output: Contribution to journalArticlepeer-review

Abstract

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER−). We further compared associations with ER+ and ER− subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER– breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER− breast cancer. © 2020 The Authors. Genetic Epidemiology published by Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)442-468
Number of pages27
JournalGenet. Epidemiol.
Volume44
Issue number5
DOIs
Publication statusPublished - 2020

Keywords

  • breast cancer subtype
  • causal gene
  • GWAS
  • TWAS
  • estrogen receptor
  • ALS2CR12 gene
  • Article
  • ATG10 gene
  • ATP6AP1L gene
  • cancer genetics
  • cancer risk
  • CASP8 gene
  • CRHR1 gene
  • CRHR1 IT1 gene
  • estrogen receptor negative breast cancer
  • estrogen receptor positive breast cancer
  • gene expression
  • gene identification
  • genetic association
  • genome-wide association study
  • HIST2H2BA gene
  • human
  • KANSL1 AS1 gene
  • L3MBTL3 gene
  • LRRC37A gene
  • LRRC37A2 gene
  • LRRC37A4P gene
  • MRPL23 AS1 gene
  • multigene family
  • NUDT17 gene
  • RP11 15A1.7 gene
  • RP11 250B2.5 gene
  • RP11 554A11.9 gene
  • RP11 73O6.3 gene
  • STXBP4 gene
  • transcriptome sequencing
  • tumor gene
  • ZNF155 gene
  • ZNF404 gene

Fingerprint Dive into the research topics of 'Transcriptome-wide association study of breast cancer risk by estrogen-receptor status: Genetic Epidemiology'. Together they form a unique fingerprint.

Cite this