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

Helian Feng; Alexander Gusev; Bogdan Pasaniuc; Lang Wu; Jirong Long; Zomoroda Abu-full; Kristiina Aittomäki; Irene L. Andrulis; Hoda Anton-Culver; Antonis C. Antoniou; Adalgeir Arason; Volker Arndt; Kristan J. Aronson; Banu K. Arun; Ella Asseryanis; Paul L. Auer; Jacopo Azzollini; Judith Balmaña; Rosa B. Barkardottir; Daniel R. Barnes; Daniel Barrowdale; Matthias W. Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Katarzyna Białkowska; Ana Blanco; Carl Blomqvist; Bram Boeckx; Natalia V. Bogdanova; Stig E. Bojesen; Manjeet K. Bolla; Bernardo Bonanni; Ake Borg; Hiltrud Brauch; Hermann Brenner; Ignacio Briceno; Annegien Broeks; Thomas Brüning; Barbara Burwinkel; Qiuyin Cai; Trinidad Caldés; Maria A. Caligo; Ian Campbell; Sander Canisius; Daniele Campa; Brian D. Carter; Jonathan Carter; Jose E. Castelao; Jenny Chang-Claude; Stephen J. Chanock; Hans Christiansen; Wendy K. Chung; Kathleen B.M. Claes; Christine L. Clarke; Fergus J. Couch; Angela Cox; Simon S. Cross; Cezary Cybulski; Kamila Czene; Mary B. Daly; Miguel de la Hoya; Kim De Leeneer; Joe Dennis; Peter Devilee; Orland Diez; Susan M. Domchek; Thilo Dörk; Isabel dos-Santos-Silva; Alison M. Dunning; Miriam Dwek; Diana M. Eccles; Bent Ejlertsen; Carolina Ellberg; Christoph Engel; Mikael Eriksson; Peter A. Fasching; Olivia Fletcher; Henrik Flyger; Florentia Fostira; Eitan Friedman; Lin Fritschi; Debra Frost; Marike Gabrielson; Patricia A. Ganz; Susan M. Gapstur; Judy Garber; Montserrat García-Closas; José A. 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; Ute Hamann; Christopher Hake; Wei He; Jane Heyworth; Frans B.L. Hogervorst; Antoinette Hollestelle; Maartje J. Hooning; Robert N. Hoover; John L. Hopper; Guanmengqian Huang; Peter J. Hulick; Keith Humphreys; Evgeny N. Imyanitov; Claudine Isaacs; Milena Jakimovska; Anna Jakubowska; Paul James; Ramunas Janavicius; Rachel C. Jankowitz; Esther M. John; Nichola Johnson; Vijai Joseph; Audrey Jung; Beth Y. Karlan; Elza Khusnutdinova; Johanna I. Kiiski; Irene Konstantopoulou; Vessela N. Kristensen; Yael Laitman; Diether Lambrechts; Conxi Lazaro; Dominique Leroux; Goska Leslie; Jenny Lester; Fabienne Lesueur; Noralane Lindor; Sara Lindström; Wing Yee Lo; Jennifer T. Loud; Jan Lubiński; Enes Makalic; Arto Mannermaa; Mehdi Manoochehri; Siranoush Manoukian; Sara Margolin; John W.M. Martens; Maria E. Martinez; Laura Matricardi; Tabea Maurer; Dimitrios Mavroudis; Lesley McGuffog; Alfons Meindl; Usha Menon; Kyriaki Michailidou; Pooja M. Kapoor; Austin Miller; Marco Montagna; Fernando Moreno; Lidia Moserle; Anna M. Mulligan; Taru A. Muranen; Katherine L. Nathanson; Susan L. Neuhausen; Heli Nevanlinna; Ines Nevelsteen; Finn C. Nielsen; Liene Nikitina-Zake; Kenneth Offit; Edith Olah; Olufunmilayo I. Olopade; Håkan Olsson; Ana Osorio; Janos Papp; Tjoung Won Park-Simon; Michael T. Parsons; Inge S. Pedersen; Ana Peixoto; Paolo Peterlongo; Julian Peto; Paul D.P. Pharoah; Kelly Anne Phillips; Dijana Plaseska-Karanfilska; Bruce Poppe; Nisha Pradhan; Karolina Prajzendanc; Nadege Presneau; Kevin Punie; Katri Pylkäs; Paolo Radice; Johanna Rantala; Muhammad Usman Rashid; Gad Rennert; Harvey A. Risch; Mark Robson; Atocha Romero; Emmanouil Saloustros; Dale P. Sandler; Catarina Santos; Elinor J. Sawyer; Marjanka K. Schmidt; Daniel F. Schmidt; Rita K. Schmutzler; Minouk J. Schoemaker; Rodney J. Scott; Priyanka Sharma; Xiao Ou Shu; Jacques Simard; Christian F. Singer; Anne Bine Skytte; Penny Soucy; Melissa C. Southey; John J. Spinelli; Amanda B. Spurdle; Jennifer Stone; Anthony J. Swerdlow; William J. Tapper; Jack A. Taylor; Manuel R. Teixeira; Mary Beth Terry; Alex Teulé; Mads Thomassen; Kathrin Thöne; Darcy L. Thull; Marc Tischkowitz; Amanda E. Toland; Rob A.E.M. Tollenaar; 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; Paula Vieiro-Balo; Qin Wang; Barbara Wappenschmidt; Clarice R. Weinberg; Jeffrey N. Weitzel; Camilla Wendt; Robert Winqvist; Xiaohong R. Yang; Drakoulis Yannoukakos; Argyrios Ziogas; Roger L. Milne; Douglas F. Easton; Georgia Chenevix-Trench; Wei Zheng; ABCTB Investigators; HEBON Investigators; BCFR Investigators; OCGN Investigators; GEMO Study Collaborators; EMBRACE Collaborators; GC-HBOC Study Collaborators

doi:10.1002/gepi.22288

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

Helian Feng, Alexander Gusev, Bogdan Pasaniuc, Lang Wu, Jirong Long, Zomoroda Abu-full, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Adalgeir Arason, Volker Arndt, Kristan J. Aronson, Banu K. Arun, Ella Asseryanis, Paul L. Auer, Jacopo Azzollini, Judith Balmaña, Rosa B. Barkardottir, Daniel R. BarnesDaniel Barrowdale, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Katarzyna Białkowska, Ana Blanco, Carl Blomqvist, Bram Boeckx, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Ake Borg, Hiltrud Brauch, Hermann Brenner, Ignacio Briceno, Annegien Broeks, Thomas Brüning, Barbara Burwinkel, Qiuyin Cai, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Sander Canisius, Daniele Campa, Brian D. Carter, Jonathan Carter, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Hans Christiansen, Wendy K. Chung, Kathleen B.M. Claes, Christine L. Clarke, Fergus J. Couch, Angela Cox, Simon S. Cross, Cezary Cybulski, Kamila Czene, Mary B. Daly, Miguel de la Hoya, Kim De Leeneer, Joe Dennis, Peter Devilee, Orland Diez, Susan M. Domchek, Thilo Dörk, Isabel dos-Santos-Silva, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Bent Ejlertsen, Carolina Ellberg, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Florentia Fostira, Eitan Friedman, Lin Fritschi, Debra Frost, Marike Gabrielson, Patricia A. Ganz, Susan M. Gapstur, Judy Garber, Montserrat García-Closas, José A. 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, Ute Hamann, Christopher Hake, Wei He, Jane Heyworth, Frans B.L. Hogervorst, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Guanmengqian Huang, Peter J. Hulick, Keith Humphreys, Evgeny N. Imyanitov, Claudine Isaacs, Milena Jakimovska, Anna Jakubowska, Paul James, Ramunas Janavicius, Rachel C. Jankowitz, Esther M. John, Nichola Johnson, Vijai Joseph, Audrey Jung, Beth Y. Karlan, Elza Khusnutdinova, Johanna I. Kiiski, Irene Konstantopoulou, Vessela N. Kristensen, Yael Laitman, Diether Lambrechts, Conxi Lazaro, Dominique Leroux, Goska Leslie, Jenny Lester, Fabienne Lesueur, Noralane Lindor, Sara Lindström, Wing Yee Lo, Jennifer T. Loud, Jan Lubiński, Enes Makalic, Arto Mannermaa, Mehdi Manoochehri, Siranoush Manoukian, Sara Margolin, John W.M. Martens, Maria E. Martinez, Laura Matricardi, Tabea Maurer, Dimitrios Mavroudis, Lesley McGuffog, Alfons Meindl, Usha Menon, Kyriaki Michailidou, Pooja M. Kapoor, Austin Miller, Marco Montagna, Fernando Moreno, Lidia Moserle, Anna M. Mulligan, Taru A. Muranen, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Ines Nevelsteen, Finn C. Nielsen, Liene Nikitina-Zake, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Håkan Olsson, Ana Osorio, Janos Papp, Tjoung Won Park-Simon, Michael T. Parsons, Inge S. Pedersen, Ana Peixoto, Paolo Peterlongo, Julian Peto, Paul D.P. Pharoah, Kelly Anne Phillips, Dijana Plaseska-Karanfilska, Bruce Poppe, Nisha Pradhan, Karolina Prajzendanc, Nadege Presneau, Kevin Punie, Katri Pylkäs, Paolo Radice, Johanna Rantala, Muhammad Usman Rashid, Gad Rennert, Harvey A. Risch, Mark Robson, Atocha Romero, Emmanouil Saloustros, Dale P. Sandler, Catarina Santos, Elinor J. Sawyer, Marjanka K. Schmidt, Daniel F. Schmidt, Rita K. Schmutzler, Minouk J. Schoemaker, Rodney J. Scott, Priyanka Sharma, Xiao Ou Shu, Jacques Simard, Christian F. Singer, Anne Bine Skytte, Penny Soucy, Melissa C. Southey, John J. Spinelli, Amanda B. Spurdle, Jennifer Stone, Anthony J. Swerdlow, William J. Tapper, Jack A. Taylor, Manuel R. Teixeira, Mary Beth Terry, Alex Teulé, Mads Thomassen, Kathrin Thöne, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Rob A.E.M. Tollenaar, 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, Paula Vieiro-Balo, Qin Wang, Barbara Wappenschmidt, Clarice R. Weinberg, Jeffrey N. Weitzel, Camilla Wendt, Robert Winqvist, Xiaohong R. Yang, Drakoulis Yannoukakos, Argyrios Ziogas, Roger L. Milne, Douglas F. Easton, Georgia Chenevix-Trench, Wei Zheng, ABCTB Investigators, HEBON Investigators, BCFR Investigators, OCGN Investigators, GEMO Study Collaborators, EMBRACE Collaborators, GC-HBOC Study Collaborators

Research output: Contribution to journal › Article › Research › peer-review

17 Citations (Scopus)

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.

Original language	English
Pages (from-to)	442-468
Number of pages	27
Journal	Genetic Epidemiology
Volume	44
Issue number	5
DOIs	https://doi.org/10.1002/gepi.22288
Publication status	Published - Jul 2020

Keywords

breast cancer subtype
causal gene
GWAS
TWAS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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311730494-oa-in pressAccepted author manuscript, 2.48 MBLicence: CC BY

Cite this

Feng, H., Gusev, A., Pasaniuc, B., Wu, L., Long, J., Abu-full, Z., Aittomäki, K., Andrulis, I. L., Anton-Culver, H., Antoniou, A. C., Arason, A., Arndt, V., Aronson, K. J., Arun, B. K., Asseryanis, E., Auer, P. L., Azzollini, J., Balmaña, J., Barkardottir, R. B., ... GC-HBOC Study Collaborators (2020). Transcriptome-wide association study of breast cancer risk by estrogen-receptor status. Genetic Epidemiology, 44(5), 442-468. https://doi.org/10.1002/gepi.22288

@article{996cef173d534482a5d885abfb85321a,

title = "Transcriptome-wide association study of breast cancer risk by estrogen-receptor status",

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.",

keywords = "breast cancer subtype, causal gene, GWAS, TWAS",

author = "Helian Feng and Alexander Gusev and Bogdan Pasaniuc and Lang Wu and Jirong Long and Zomoroda Abu-full and Kristiina Aittom{\"a}ki and Andrulis, {Irene L.} and Hoda Anton-Culver and Antoniou, {Antonis C.} and Adalgeir Arason and Volker Arndt and Aronson, {Kristan J.} and Arun, {Banu K.} and Ella Asseryanis and Auer, {Paul L.} and Jacopo Azzollini and Judith Balma{\~n}a and Barkardottir, {Rosa B.} and Barnes, {Daniel R.} and Daniel Barrowdale and Beckmann, {Matthias W.} and Sabine Behrens and Javier Benitez and Marina Bermisheva and Katarzyna Bia{\l}kowska and Ana Blanco and Carl Blomqvist and Bram Boeckx and Bogdanova, {Natalia V.} and Bojesen, {Stig E.} and Bolla, {Manjeet K.} and Bernardo Bonanni and Ake Borg and Hiltrud Brauch and Hermann Brenner and Ignacio Briceno and Annegien Broeks and Thomas Br{\"u}ning and Barbara Burwinkel and Qiuyin Cai and Trinidad Cald{\'e}s and Caligo, {Maria A.} and Ian Campbell and Sander Canisius and Daniele Campa and Carter, {Brian D.} and Jonathan Carter and Castelao, {Jose E.} and Jenny Chang-Claude and Chanock, {Stephen J.} and Hans Christiansen and Chung, {Wendy K.} and Claes, {Kathleen B.M.} and Clarke, {Christine L.} and Couch, {Fergus J.} and Angela Cox and Cross, {Simon S.} and Cezary Cybulski and Kamila Czene and Daly, {Mary B.} and {de la Hoya}, Miguel and {De Leeneer}, Kim and Joe Dennis and Peter Devilee and Orland Diez and Domchek, {Susan M.} and Thilo D{\"o}rk and Isabel dos-Santos-Silva and Dunning, {Alison M.} and Miriam Dwek and Eccles, {Diana M.} and Bent Ejlertsen and Carolina Ellberg and Christoph Engel and Mikael Eriksson and Fasching, {Peter A.} and Olivia Fletcher and Henrik Flyger and Florentia Fostira and Eitan Friedman and Lin Fritschi and Debra Frost and Marike Gabrielson and Ganz, {Patricia A.} and Gapstur, {Susan M.} and Judy Garber and Montserrat Garc{\'i}a-Closas and Garc{\'i}a-S{\'a}enz, {Jos{\'e} A.} and Gaudet, {Mia M.} and Giles, {Graham G.} and Gord Glendon and Godwin, {Andrew K.} and Goldberg, {Mark S.} and Goldgar, {David E.} and Anna Gonz{\'a}lez-Neira and Greene, {Mark H.} and Jacek Gronwald and Pascal Gu{\'e}nel and Haiman, {Christopher A.} and Per Hall and Ute Hamann and Christopher Hake and Wei He and Jane Heyworth and Hogervorst, {Frans B.L.} and Antoinette Hollestelle and Hooning, {Maartje J.} and Hoover, {Robert N.} and Hopper, {John L.} and Guanmengqian Huang and Hulick, {Peter J.} and Keith Humphreys and Imyanitov, {Evgeny N.} and Claudine Isaacs and Milena Jakimovska and Anna Jakubowska and Paul James and Ramunas Janavicius and Jankowitz, {Rachel C.} and John, {Esther M.} and Nichola Johnson and Vijai Joseph and Audrey Jung and Karlan, {Beth Y.} and Elza Khusnutdinova and Kiiski, {Johanna I.} and Irene Konstantopoulou and Kristensen, {Vessela N.} and Yael Laitman and Diether Lambrechts and Conxi Lazaro and Dominique Leroux and Goska Leslie and Jenny Lester and Fabienne Lesueur and Noralane Lindor and Sara Lindstr{\"o}m and Lo, {Wing Yee} and Loud, {Jennifer T.} and Jan Lubi{\'n}ski and Enes Makalic and Arto Mannermaa and Mehdi Manoochehri and Siranoush Manoukian and Sara Margolin and Martens, {John W.M.} and Martinez, {Maria E.} and Laura Matricardi and Tabea Maurer and Dimitrios Mavroudis and Lesley McGuffog and Alfons Meindl and Usha Menon and Kyriaki Michailidou and Kapoor, {Pooja M.} and Austin Miller and Marco Montagna and Fernando Moreno and Lidia Moserle and Mulligan, {Anna M.} and Muranen, {Taru A.} and Nathanson, {Katherine L.} and Neuhausen, {Susan L.} and Heli Nevanlinna and Ines Nevelsteen and Nielsen, {Finn C.} and Liene Nikitina-Zake and Kenneth Offit and Edith Olah and Olopade, {Olufunmilayo I.} and H{\aa}kan Olsson and Ana Osorio and Janos Papp and Park-Simon, {Tjoung Won} and Parsons, {Michael T.} and Pedersen, {Inge S.} and Ana Peixoto and Paolo Peterlongo and Julian Peto and Pharoah, {Paul D.P.} and Phillips, {Kelly Anne} and Dijana Plaseska-Karanfilska and Bruce Poppe and Nisha Pradhan and Karolina Prajzendanc and Nadege Presneau and Kevin Punie and Katri Pylk{\"a}s and Paolo Radice and Johanna Rantala and Rashid, {Muhammad Usman} and Gad Rennert and Risch, {Harvey A.} and Mark Robson and Atocha Romero and Emmanouil Saloustros and Sandler, {Dale P.} and Catarina Santos and Sawyer, {Elinor J.} and Schmidt, {Marjanka K.} and Schmidt, {Daniel F.} and Schmutzler, {Rita K.} and Schoemaker, {Minouk J.} and Scott, {Rodney J.} and Priyanka Sharma and Shu, {Xiao Ou} and Jacques Simard and Singer, {Christian F.} and Skytte, {Anne Bine} and Penny Soucy and Southey, {Melissa C.} and Spinelli, {John J.} and Spurdle, {Amanda B.} and Jennifer Stone and Swerdlow, {Anthony J.} and Tapper, {William J.} and Taylor, {Jack A.} and Teixeira, {Manuel R.} and Terry, {Mary Beth} and Alex Teul{\'e} and Mads Thomassen and Kathrin Th{\"o}ne and Thull, {Darcy L.} and Marc Tischkowitz and Toland, {Amanda E.} and Tollenaar, {Rob A.E.M.} and Diana Torres and Th{\'e}r{\`e}se Truong and Nadine Tung and Vachon, {Celine M.} and {van Asperen}, {Christi J.} and {van den Ouweland}, {Ans M.W.} and {van Rensburg}, {Elizabeth J.} and Ana Vega and Alessandra Viel and Paula Vieiro-Balo and Qin Wang and Barbara Wappenschmidt and Weinberg, {Clarice R.} and Weitzel, {Jeffrey N.} and Camilla Wendt and Robert Winqvist and Yang, {Xiaohong R.} and Drakoulis Yannoukakos and Argyrios Ziogas and Milne, {Roger L.} and Easton, {Douglas F.} and Georgia Chenevix-Trench and Wei Zheng and {ABCTB Investigators} and {HEBON Investigators} and {BCFR Investigators} and {OCGN Investigators} and {GEMO Study Collaborators} and {EMBRACE Collaborators} and {GC-HBOC Study Collaborators}",

year = "2020",

month = jul,

doi = "10.1002/gepi.22288",

language = "English",

volume = "44",

pages = "442--468",

journal = "Genetic Epidemiology",

issn = "0741-0395",

publisher = "John Wiley & Sons",

number = "5",

}

Feng, H, Gusev, A, Pasaniuc, B, Wu, L, Long, J, Abu-full, Z, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Arason, A, Arndt, V, Aronson, KJ, Arun, BK, Asseryanis, E, Auer, PL, Azzollini, J, Balmaña, J, Barkardottir, RB, Barnes, DR, Barrowdale, D, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Białkowska, K, Blanco, A, Blomqvist, C, Boeckx, B, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Borg, A, Brauch, H, Brenner, H, Briceno, I, Broeks, A, Brüning, T, Burwinkel, B, Cai, Q, Caldés, T, Caligo, MA, Campbell, I, Canisius, S, Campa, D, Carter, BD, Carter, J, Castelao, JE, Chang-Claude, J, Chanock, SJ, Christiansen, H, Chung, WK, Claes, KBM, Clarke, CL, Couch, FJ, Cox, A, Cross, SS, Cybulski, C, Czene, K, Daly, MB, de la Hoya, M, De Leeneer, K, Dennis, J, Devilee, P, Diez, O, Domchek, SM, Dörk, T, dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Ejlertsen, B, Ellberg, C, Engel, C, Eriksson, M, Fasching, PA, Fletcher, O, Flyger, H, Fostira, F, Friedman, E, Fritschi, L, Frost, D, Gabrielson, M, Ganz, PA, Gapstur, SM, Garber, J, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Gronwald, J, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hake, C, He, W, Heyworth, J, Hogervorst, FBL, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Huang, G, Hulick, PJ, Humphreys, K, Imyanitov, EN, Isaacs, C, Jakimovska, M, Jakubowska, A, James, P, Janavicius, R, Jankowitz, RC, John, EM, Johnson, N, Joseph, V, Jung, A, Karlan, BY, Khusnutdinova, E, Kiiski, JI, Konstantopoulou, I, Kristensen, VN, Laitman, Y, Lambrechts, D, Lazaro, C, Leroux, D, Leslie, G, Lester, J, Lesueur, F, Lindor, N, Lindström, S, Lo, WY, Loud, JT, Lubiński, J, Makalic, E, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Martens, JWM, Martinez, ME, Matricardi, L, Maurer, T, Mavroudis, D, McGuffog, L, Meindl, A, Menon, U, Michailidou, K, Kapoor, PM, Miller, A, Montagna, M, Moreno, F, Moserle, L, Mulligan, AM, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nevelsteen, I, Nielsen, FC, Nikitina-Zake, L, Offit, K, Olah, E, Olopade, OI, Olsson, H, Osorio, A, Papp, J, Park-Simon, TW, Parsons, MT, Pedersen, IS, Peixoto, A, Peterlongo, P, Peto, J, Pharoah, PDP, Phillips, KA, Plaseska-Karanfilska, D, Poppe, B, Pradhan, N, Prajzendanc, K, Presneau, N, Punie, K, Pylkäs, K, Radice, P, Rantala, J, Rashid, MU, Rennert, G, Risch, HA, Robson, M, Romero, A, Saloustros, E, Sandler, DP, Santos, C, Sawyer, EJ, Schmidt, MK, Schmidt, DF, Schmutzler, RK, Schoemaker, MJ, Scott, RJ, Sharma, P, Shu, XO, Simard, J, Singer, CF, Skytte, AB, Soucy, P, Southey, MC, Spinelli, JJ, Spurdle, AB, Stone, J, Swerdlow, AJ, Tapper, WJ, Taylor, JA, Teixeira, MR, Terry, MB, Teulé, A, Thomassen, M, Thöne, K, Thull, DL, Tischkowitz, M, Toland, AE, Tollenaar, RAEM, Torres, D, Truong, T, Tung, N, Vachon, CM, van Asperen, CJ, van den Ouweland, AMW, van Rensburg, EJ, Vega, A, Viel, A, Vieiro-Balo, P, Wang, Q, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wendt, C, Winqvist, R, Yang, XR, Yannoukakos, D, Ziogas, A, Milne, RL, Easton, DF, Chenevix-Trench, G, Zheng, W, ABCTB Investigators, HEBON Investigators, BCFR Investigators, OCGN Investigators, GEMO Study Collaborators, EMBRACE Collaborators & GC-HBOC Study Collaborators 2020, 'Transcriptome-wide association study of breast cancer risk by estrogen-receptor status', Genetic Epidemiology, vol. 44, no. 5, pp. 442-468. https://doi.org/10.1002/gepi.22288

TY - JOUR

T1 - Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

AU - Feng, Helian

AU - Gusev, Alexander

AU - Pasaniuc, Bogdan

AU - Wu, Lang

AU - Long, Jirong

AU - Abu-full, Zomoroda

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Antoniou, Antonis C.

AU - Arason, Adalgeir

AU - Arndt, Volker

AU - Aronson, Kristan J.

AU - Arun, Banu K.

AU - Asseryanis, Ella

AU - Auer, Paul L.

AU - Azzollini, Jacopo

AU - Balmaña, Judith

AU - Barkardottir, Rosa B.

AU - Barnes, Daniel R.

AU - Barrowdale, Daniel

AU - Beckmann, Matthias W.

AU - Behrens, Sabine

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Białkowska, Katarzyna

AU - Blanco, Ana

AU - Blomqvist, Carl

AU - Boeckx, Bram

AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Bolla, Manjeet K.

AU - Bonanni, Bernardo

AU - Borg, Ake

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Briceno, Ignacio

AU - Broeks, Annegien

AU - Brüning, Thomas

AU - Burwinkel, Barbara

AU - Cai, Qiuyin

AU - Caldés, Trinidad

AU - Caligo, Maria A.

AU - Campbell, Ian

AU - Canisius, Sander

AU - Campa, Daniele

AU - Carter, Brian D.

AU - Carter, Jonathan

AU - Castelao, Jose E.

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J.

AU - Christiansen, Hans

AU - Chung, Wendy K.

AU - Claes, Kathleen B.M.

AU - Clarke, Christine L.

AU - Couch, Fergus J.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Cybulski, Cezary

AU - Czene, Kamila

AU - Daly, Mary B.

AU - de la Hoya, Miguel

AU - De Leeneer, Kim

AU - Dennis, Joe

AU - Devilee, Peter

AU - Diez, Orland

AU - Domchek, Susan M.

AU - Dörk, Thilo

AU - dos-Santos-Silva, Isabel

AU - Dunning, Alison M.

AU - Dwek, Miriam

AU - Eccles, Diana M.

AU - Ejlertsen, Bent

AU - Ellberg, Carolina

AU - Engel, Christoph

AU - Eriksson, Mikael

AU - Fasching, Peter A.

AU - Fletcher, Olivia

AU - Flyger, Henrik

AU - Fostira, Florentia

AU - Friedman, Eitan

AU - Fritschi, Lin

AU - Frost, Debra

AU - Gabrielson, Marike

AU - Ganz, Patricia A.

AU - Gapstur, Susan M.

AU - Garber, Judy

AU - García-Closas, Montserrat

AU - García-Sáenz, José A.

AU - Gaudet, Mia M.

AU - Giles, Graham G.

AU - Glendon, Gord

AU - Godwin, Andrew K.

AU - Goldberg, Mark S.

AU - Goldgar, David E.

AU - González-Neira, Anna

AU - Greene, Mark H.

AU - Gronwald, Jacek

AU - Guénel, Pascal

AU - Haiman, Christopher A.

AU - Hall, Per

AU - Hamann, Ute

AU - Hake, Christopher

AU - He, Wei

AU - Heyworth, Jane

AU - Hogervorst, Frans B.L.

AU - Hollestelle, Antoinette

AU - Hooning, Maartje J.

AU - Hoover, Robert N.

AU - Hopper, John L.

AU - Huang, Guanmengqian

AU - Hulick, Peter J.

AU - Humphreys, Keith

AU - Imyanitov, Evgeny N.

AU - Isaacs, Claudine

AU - Jakimovska, Milena

AU - Jakubowska, Anna

AU - James, Paul

AU - Janavicius, Ramunas

AU - Jankowitz, Rachel C.

AU - John, Esther M.

AU - Johnson, Nichola

AU - Joseph, Vijai

AU - Jung, Audrey

AU - Karlan, Beth Y.

AU - Khusnutdinova, Elza

AU - Kiiski, Johanna I.

AU - Konstantopoulou, Irene

AU - Kristensen, Vessela N.

AU - Laitman, Yael

AU - Lambrechts, Diether

AU - Lazaro, Conxi

AU - Leroux, Dominique

AU - Leslie, Goska

AU - Lester, Jenny

AU - Lesueur, Fabienne

AU - Lindor, Noralane

AU - Lindström, Sara

AU - Lo, Wing Yee

AU - Loud, Jennifer T.

AU - Lubiński, Jan

AU - Makalic, Enes

AU - Mannermaa, Arto

AU - Manoochehri, Mehdi

AU - Manoukian, Siranoush

AU - Margolin, Sara

AU - Martens, John W.M.

AU - Martinez, Maria E.

AU - Matricardi, Laura

AU - Maurer, Tabea

AU - Mavroudis, Dimitrios

AU - McGuffog, Lesley

AU - Meindl, Alfons

AU - Menon, Usha

AU - Michailidou, Kyriaki

AU - Kapoor, Pooja M.

AU - Miller, Austin

AU - Montagna, Marco

AU - Moreno, Fernando

AU - Moserle, Lidia

AU - Mulligan, Anna M.

AU - Muranen, Taru A.

AU - Nathanson, Katherine L.

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Nevelsteen, Ines

AU - Nielsen, Finn C.

AU - Nikitina-Zake, Liene

AU - Offit, Kenneth

AU - Olah, Edith

AU - Olopade, Olufunmilayo I.

AU - Olsson, Håkan

AU - Osorio, Ana

AU - Papp, Janos

AU - Park-Simon, Tjoung Won

AU - Parsons, Michael T.

AU - Pedersen, Inge S.

AU - Peixoto, Ana

AU - Peterlongo, Paolo

AU - Peto, Julian

AU - Pharoah, Paul D.P.

AU - Phillips, Kelly Anne

AU - Plaseska-Karanfilska, Dijana

AU - Poppe, Bruce

AU - Pradhan, Nisha

AU - Prajzendanc, Karolina

AU - Presneau, Nadege

AU - Punie, Kevin

AU - Pylkäs, Katri

AU - Radice, Paolo

AU - Rantala, Johanna

AU - Rashid, Muhammad Usman

AU - Rennert, Gad

AU - Risch, Harvey A.

AU - Robson, Mark

AU - Romero, Atocha

AU - Saloustros, Emmanouil

AU - Sandler, Dale P.

AU - Santos, Catarina

AU - Sawyer, Elinor J.

AU - Schmidt, Marjanka K.

AU - Schmidt, Daniel F.

AU - Schmutzler, Rita K.

AU - Schoemaker, Minouk J.

AU - Scott, Rodney J.

AU - Sharma, Priyanka

AU - Shu, Xiao Ou

AU - Simard, Jacques

AU - Singer, Christian F.

AU - Skytte, Anne Bine

AU - Soucy, Penny

AU - Southey, Melissa C.

AU - Spinelli, John J.

AU - Spurdle, Amanda B.

AU - Stone, Jennifer

AU - Swerdlow, Anthony J.

AU - Tapper, William J.

AU - Taylor, Jack A.

AU - Teixeira, Manuel R.

AU - Terry, Mary Beth

AU - Teulé, Alex

AU - Thomassen, Mads

AU - Thöne, Kathrin

AU - Thull, Darcy L.

AU - Tischkowitz, Marc

AU - Toland, Amanda E.

AU - Tollenaar, Rob A.E.M.

AU - Torres, Diana

AU - Truong, Thérèse

AU - Tung, Nadine

AU - Vachon, Celine M.

AU - van Asperen, Christi J.

AU - van den Ouweland, Ans M.W.

AU - van Rensburg, Elizabeth J.

AU - Vega, Ana

AU - Viel, Alessandra

AU - Vieiro-Balo, Paula

AU - Wang, Qin

AU - Wappenschmidt, Barbara

AU - Weinberg, Clarice R.

AU - Weitzel, Jeffrey N.

AU - Wendt, Camilla

AU - Winqvist, Robert

AU - Yang, Xiaohong R.

AU - Yannoukakos, Drakoulis

AU - Ziogas, Argyrios

AU - Milne, Roger L.

AU - Easton, Douglas F.

AU - Chenevix-Trench, Georgia

AU - Zheng, Wei

AU - ABCTB Investigators

AU - HEBON Investigators

AU - BCFR Investigators

AU - OCGN Investigators

AU - GEMO Study Collaborators

AU - EMBRACE Collaborators

AU - GC-HBOC Study Collaborators

PY - 2020/7

Y1 - 2020/7

N2 - 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.

AB - 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.

KW - breast cancer subtype

KW - causal gene

KW - GWAS

KW - TWAS

UR - http://www.scopus.com/inward/record.url?scp=85081379482&partnerID=8YFLogxK

U2 - 10.1002/gepi.22288

DO - 10.1002/gepi.22288

M3 - Article

C2 - 32115800

AN - SCOPUS:85081379482

VL - 44

SP - 442

EP - 468

JO - Genetic Epidemiology

JF - Genetic Epidemiology

SN - 0741-0395

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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