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

Manuel A. Ferreira; Adalgeir Arason; Eric R Gamazon; Fares Al-Ejeh; Kristiina Aittomäki; Irene L Andrulis; Hoda Anton-Culver; Volker Arndt; Kristan J Aronson; Banu K Arun; Ella Asseryanis; Jacopo Azzollini; Judith Balmaña; Daniel R Barnes; Daniel Barrowdale; Matthias W Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Katarzyna Białkowska; Carl Blomqvist; Natalia V Bogdanova; Stig E Bojesen; Manjeet K Bolla; Ake 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 B M Claes; Christine L Clarke; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; Mary B Daly; Miguel De la Hoya; Joe Dennis; Peter Devilee; Orland Diez; Thilo Dörk; Alison M Dunning; Miriam Dwek; Diana M Eccles; Bent Ejlertsen; Carolina Ellberg; Christoph Engel; Mikael Eriksson; Peter A Fasching; Olivia Fletcher; Henrik Flyger; Eitan Friedman; Debra Frost; Marike Gabrielson; Manuela Gago-Dominguez; 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; Wei He; Jane Heyworth; Frans B L Hogervorst; Antoinette Hollestelle; Robert N Hoover; John L Hopper; Peter J Hulick; Keith Humphreys; Evgeny N Imyanitov; Claudine Isaacs; Milena Jakimovska; Anna Jakubowska; Paul A James; Ramunas Janavicius; Rachel C Jankowitz; Esther M John; Nichola Johnson; Vijai Joseph; Beth Y Karlan; Elza Khusnutdinova; Johanna I Kiiski; Yon-Dschun Ko; Michael E Jones; Irene Konstantopoulou; Vessela N Kristensen; Yael Laitman; Diether Lambrechts; Conxi Lazaro; Goska Leslie; Jenny Lester; Fabienne Lesueur; Sara Lindström; Jirong Long; Jennifer T Loud; Jan Lubiński; Enes Makalic; Arto Mannermaa; 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 Nikitina-Zake; Robert L Nussbaum; Kenneth Offit; Edith Olah; Olufunmilayo I Olopade; Håkan Olsson; Ana Osorio; Janos Papp; Tjoung-Won Park-Simon; Michael T Parsons; Inge Sokilde Pedersen; Ana Peixoto; Paolo Peterlongo; Paul D P Pharoah; Dijana Plaseska-Karanfilska; Bruce Poppe; Nadege 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 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; 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; Jonathan Beesley; Georgia Chenevix-Trench

doi:10.1038/s41467-018-08053-5

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

Manuel A. Ferreira, Adalgeir Arason, Eric R Gamazon, Fares Al-Ejeh, Kristiina Aittomäki, Irene L Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J Aronson, Banu K Arun, Ella Asseryanis, Jacopo Azzollini, Judith Balmaña, Daniel R Barnes, Daniel Barrowdale, Matthias W Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Katarzyna BiałkowskaCarl Blomqvist, Natalia V Bogdanova, Stig E Bojesen, Manjeet K Bolla, Ake 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 B M Claes, Christine L Clarke, Fergus J Couch, Angela Cox, Simon S Cross, Kamila Czene, Mary B Daly, Miguel De la Hoya, Joe Dennis, Peter Devilee, Orland Diez, Thilo Dörk, Alison M Dunning, Miriam Dwek, Diana M Eccles, Bent Ejlertsen, Carolina Ellberg, Christoph Engel, Mikael Eriksson, Peter A Fasching, Olivia Fletcher, Henrik Flyger, Eitan Friedman, Debra Frost, Marike Gabrielson, Manuela Gago-Dominguez, 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, Wei He, Jane Heyworth, Frans B L Hogervorst, Antoinette Hollestelle, Robert N Hoover, John L Hopper, Peter J Hulick, Keith Humphreys, Evgeny N Imyanitov, Claudine Isaacs, Milena Jakimovska, Anna Jakubowska, Paul A James, Ramunas Janavicius, Rachel C Jankowitz, Esther M John, Nichola Johnson, Vijai Joseph, Beth Y Karlan, Elza Khusnutdinova, Johanna I Kiiski, Yon-Dschun Ko, Michael E Jones, Irene Konstantopoulou, Vessela N Kristensen, Yael Laitman, Diether Lambrechts, Conxi Lazaro, Goska Leslie, Jenny Lester, Fabienne Lesueur, Sara Lindström, Jirong Long, Jennifer T Loud, Jan Lubiński, Enes Makalic, Arto Mannermaa, 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 Nikitina-Zake, Robert L Nussbaum, Kenneth Offit, Edith Olah, Olufunmilayo I Olopade, Håkan Olsson, Ana Osorio, Janos Papp, Tjoung-Won Park-Simon, Michael T Parsons, Inge Sokilde Pedersen, Ana Peixoto, Paolo Peterlongo, Paul D P Pharoah, Dijana Plaseska-Karanfilska, Bruce Poppe, Nadege 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 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, 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, Jonathan Beesley, Georgia Chenevix-Trench

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

21 Citations (Scopus)

Abstract

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.

Original language	English
Number of pages	1741
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08053-5
Publication status	Published - 15 Apr 2019

Other keywords

Cancer
Genetics
Krabbamein
Erfðafræði
Brjóstakrabbamein
Erfðarannsóknir
Gen
Breast Neoplasms
Genome-Wide Association Study

Access to Document

10.1038/s41467-018-08053-5

Cite this

Ferreira, M. A., Arason, A., Gamazon, E. R., Al-Ejeh, F., Aittomäki, K., Andrulis, I. L., Anton-Culver, H., Arndt, V., Aronson, K. J., Arun, B. K., Asseryanis, E., Azzollini, J., Balmaña, J., Barnes, D. R., Barrowdale, D., Beckmann, M. W., Behrens, S., Benitez, J., Bermisheva, M., ... Chenevix-Trench, G. (2019). Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. Nature Communications, 10(1). https://doi.org/10.1038/s41467-018-08053-5

@article{48527db222004c6bb180d43bfe4b3404,

title = "Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer",

abstract = "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.",

keywords = "Cancer, Genetics, Krabbamein, Erf{\dh}afr{\ae}{\dh}i, Brj{\'o}stakrabbamein, Erf{\dh}aranns{\'o}knir, Gen, Breast Neoplasms, Genome-Wide Association Study, Cancer, Genetics, Krabbamein, Erf{\dh}afr{\ae}{\dh}i, Brj{\'o}stakrabbamein, Erf{\dh}aranns{\'o}knir, Gen, Breast Neoplasms, Genome-Wide Association Study",

author = "Ferreira, {Manuel A.} and Adalgeir Arason and Gamazon, {Eric R} and Fares Al-Ejeh and Kristiina Aittom{\"a}ki and Andrulis, {Irene L} and Hoda Anton-Culver and Volker Arndt and Aronson, {Kristan J} and Arun, {Banu K} and Ella Asseryanis and Jacopo Azzollini and Judith Balma{\~n}a 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 Carl Blomqvist and Bogdanova, {Natalia V} and Bojesen, {Stig E} and Bolla, {Manjeet K} and Ake Borg and Hiltrud Brauch and Hermann Brenner and Annegien Broeks and Barbara Burwinkel and Trinidad Cald{\'e}s and Caligo, {Maria A} and Daniele Campa and Ian Campbell and Federico Canzian and Jonathan Carter and Carter, {Brian D} 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 Kamila Czene and Daly, {Mary B} and {De la Hoya}, Miguel and Joe Dennis and Peter Devilee and Orland Diez and Thilo D{\"o}rk 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 Eitan Friedman and Debra Frost and Marike Gabrielson and Manuela Gago-Dominguez 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 Wei He and Jane Heyworth and Hogervorst, {Frans B L} and Antoinette Hollestelle and Hoover, {Robert N} and Hopper, {John L} and Hulick, {Peter J} and Keith Humphreys and Imyanitov, {Evgeny N} and Claudine Isaacs and Milena Jakimovska and Anna Jakubowska and James, {Paul A} and Ramunas Janavicius and Jankowitz, {Rachel C} and John, {Esther M} and Nichola Johnson and Vijai Joseph and Karlan, {Beth Y} and Elza Khusnutdinova and Kiiski, {Johanna I} and Yon-Dschun Ko and Jones, {Michael E} and Irene Konstantopoulou and Kristensen, {Vessela N} and Yael Laitman and Diether Lambrechts and Conxi Lazaro and Goska Leslie and Jenny Lester and Fabienne Lesueur and Sara Lindstr{\"o}m and Jirong Long and Loud, {Jennifer T} and Jan Lubi{\'n}ski and Enes Makalic and Arto Mannermaa and Mehdi Manoochehri and Sara Margolin and Tabea Maurer and Dimitrios Mavroudis and Lesley McGuffog and Alfons Meindl and Usha Menon and Kyriaki Michailidou and Austin Miller and Marco Montagna and Fernando Moreno and Lidia Moserle and Mulligan, {Anna Marie} and Nathanson, {Katherine L} and Neuhausen, {Susan L} and Heli Nevanlinna and Ines Nevelsteen and Nielsen, {Finn C} and Liene Nikitina-Zake and Nussbaum, {Robert L} and Kenneth Offit and Edith Olah and Olopade, {Olufunmilayo I} and H{\aa}kan Olsson and Ana Osorio and Janos Papp and Tjoung-Won Park-Simon and Parsons, {Michael T} and Pedersen, {Inge Sokilde} and Ana Peixoto and Paolo Peterlongo and Pharoah, {Paul D P} and Dijana Plaseska-Karanfilska and Bruce Poppe and Nadege Presneau and Paolo Radice and Johanna Rantala and Gad Rennert and Risch, {Harvey A} and Emmanouil Saloustros and Kristin Sanden and Sawyer, {Elinor J} and Schmidt, {Marjanka K} and Schmutzler, {Rita K} and Priyanka Sharma and Xiao-Ou Shu and Jacques Simard and Singer, {Christian F} 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 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 Qin Wang and Barbara Wappenschmidt and Weitzel, {Jeffrey N} and Camilla Wendt and Robert Winqvist and Yang, {Xiaohong R} and Drakoulis Yannoukakos and Argyrios Ziogas and Peter Kraft and Antoniou, {Antonis C} and Wei Zheng and Easton, {Douglas F} and Milne, {Roger L} and Jonathan Beesley and Georgia Chenevix-Trench",

year = "2019",

month = apr,

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doi = "10.1038/s41467-018-08053-5",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

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Ferreira, MA, Arason, A, Gamazon, ER, Al-Ejeh, F, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Arun, BK, Asseryanis, E, Azzollini, J, Balmaña, J, Barnes, DR, Barrowdale, D, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Białkowska, K, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Borg, A, Brauch, H, Brenner, H, Broeks, A, Burwinkel, B, Caldés, T, Caligo, MA, Campa, D, Campbell, I, Canzian, F, Carter, J, Carter, BD, Castelao, JE, Chang-Claude, J, Chanock, SJ, Christiansen, H, Chung, WK, Claes, KBM, Clarke, CL, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, De la Hoya, M, Dennis, J, Devilee, P, Diez, O, Dörk, T, Dunning, AM, Dwek, M, Eccles, DM, Ejlertsen, B, Ellberg, C, Engel, C, Eriksson, M, Fasching, PA, Fletcher, O, Flyger, H, Friedman, E, Frost, D, Gabrielson, M, Gago-Dominguez, 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, He, W, Heyworth, J, Hogervorst, FBL, Hollestelle, A, Hoover, RN, Hopper, JL, Hulick, PJ, Humphreys, K, Imyanitov, EN, Isaacs, C, Jakimovska, M, Jakubowska, A, James, PA, Janavicius, R, Jankowitz, RC, John, EM, Johnson, N, Joseph, V, Karlan, BY, Khusnutdinova, E, Kiiski, JI, Ko, Y-D, Jones, ME, Konstantopoulou, I, Kristensen, VN, Laitman, Y, Lambrechts, D, Lazaro, C, Leslie, G, Lester, J, Lesueur, F, Lindström, S, Long, J, Loud, JT, Lubiński, J, Makalic, E, Mannermaa, A, Manoochehri, M, Margolin, S, Maurer, T, Mavroudis, D, McGuffog, L, Meindl, A, Menon, U, Michailidou, K, Miller, A, Montagna, M, Moreno, F, Moserle, L, Mulligan, AM, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nevelsteen, I, Nielsen, FC, Nikitina-Zake, L, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olsson, H, Osorio, A, Papp, J, Park-Simon, T-W, Parsons, MT, Pedersen, IS, Peixoto, A, Peterlongo, P, Pharoah, PDP, Plaseska-Karanfilska, D, Poppe, B, Presneau, N, Radice, P, Rantala, J, Rennert, G, Risch, HA, Saloustros, E, Sanden, K, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Sharma, P, Shu, X-O, Simard, J, Singer, CF, 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, Torres, D, Truong, T, Tung, N, Vachon, CM, van Asperen, CJ, van den Ouweland, AMW, van Rensburg, EJ, Vega, A, Viel, A, Wang, Q, Wappenschmidt, B, Weitzel, JN, Wendt, C, Winqvist, R, Yang, XR, Yannoukakos, D, Ziogas, A, Kraft, P, Antoniou, AC, Zheng, W, Easton, DF, Milne, RL, Beesley, J & Chenevix-Trench, G 2019, 'Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer', Nature Communications, vol. 10, no. 1. https://doi.org/10.1038/s41467-018-08053-5

TY - JOUR

T1 - Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

AU - Ferreira, Manuel A.

AU - Arason, Adalgeir

AU - Gamazon, Eric R

AU - Al-Ejeh, Fares

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Aronson, Kristan J

AU - Arun, Banu K

AU - Asseryanis, Ella

AU - Azzollini, Jacopo

AU - Balmaña, Judith

AU - Barnes, Daniel R

AU - Barrowdale, Daniel

AU - Beckmann, Matthias W

AU - Behrens, Sabine

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Białkowska, Katarzyna

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V

AU - Bojesen, Stig E

AU - Bolla, Manjeet K

AU - Borg, Ake

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Broeks, Annegien

AU - Burwinkel, Barbara

AU - Caldés, Trinidad

AU - Caligo, Maria A

AU - Campa, Daniele

AU - Campbell, Ian

AU - Canzian, Federico

AU - Carter, Jonathan

AU - Carter, Brian D

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 - Czene, Kamila

AU - Daly, Mary B

AU - De la Hoya, Miguel

AU - Dennis, Joe

AU - Devilee, Peter

AU - Diez, Orland

AU - Dörk, Thilo

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 - Friedman, Eitan

AU - Frost, Debra

AU - Gabrielson, Marike

AU - Gago-Dominguez, Manuela

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 - He, Wei

AU - Heyworth, Jane

AU - Hogervorst, Frans B L

AU - Hollestelle, Antoinette

AU - Hoover, Robert N

AU - Hopper, John L

AU - Hulick, Peter J

AU - Humphreys, Keith

AU - Imyanitov, Evgeny N

AU - Isaacs, Claudine

AU - Jakimovska, Milena

AU - Jakubowska, Anna

AU - James, Paul A

AU - Janavicius, Ramunas

AU - Jankowitz, Rachel C

AU - John, Esther M

AU - Johnson, Nichola

AU - Joseph, Vijai

AU - Karlan, Beth Y

AU - Khusnutdinova, Elza

AU - Kiiski, Johanna I

AU - Ko, Yon-Dschun

AU - Jones, Michael E

AU - Konstantopoulou, Irene

AU - Kristensen, Vessela N

AU - Laitman, Yael

AU - Lambrechts, Diether

AU - Lazaro, Conxi

AU - Leslie, Goska

AU - Lester, Jenny

AU - Lesueur, Fabienne

AU - Lindström, Sara

AU - Long, Jirong

AU - Loud, Jennifer T

AU - Lubiński, Jan

AU - Makalic, Enes

AU - Mannermaa, Arto

AU - Manoochehri, Mehdi

AU - Margolin, Sara

AU - Maurer, Tabea

AU - Mavroudis, Dimitrios

AU - McGuffog, Lesley

AU - Meindl, Alfons

AU - Menon, Usha

AU - Michailidou, Kyriaki

AU - Miller, Austin

AU - Montagna, Marco

AU - Moreno, Fernando

AU - Moserle, Lidia

AU - Mulligan, Anna Marie

AU - Nathanson, Katherine L

AU - Neuhausen, Susan L

AU - Nevanlinna, Heli

AU - Nevelsteen, Ines

AU - Nielsen, Finn C

AU - Nikitina-Zake, Liene

AU - Nussbaum, Robert L

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 Sokilde

AU - Peixoto, Ana

AU - Peterlongo, Paolo

AU - Pharoah, Paul D P

AU - Plaseska-Karanfilska, Dijana

AU - Poppe, Bruce

AU - Presneau, Nadege

AU - Radice, Paolo

AU - Rantala, Johanna

AU - Rennert, Gad

AU - Risch, Harvey A

AU - Saloustros, Emmanouil

AU - Sanden, Kristin

AU - Sawyer, Elinor J

AU - Schmidt, Marjanka K

AU - Schmutzler, Rita K

AU - Sharma, Priyanka

AU - Shu, Xiao-Ou

AU - Simard, Jacques

AU - Singer, Christian F

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 - 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 - Wang, Qin

AU - Wappenschmidt, Barbara

AU - Weitzel, Jeffrey N

AU - Wendt, Camilla

AU - Winqvist, Robert

AU - Yang, Xiaohong R

AU - Yannoukakos, Drakoulis

AU - Ziogas, Argyrios

AU - Kraft, Peter

AU - Antoniou, Antonis C

AU - Zheng, Wei

AU - Easton, Douglas F

AU - Milne, Roger L

AU - Beesley, Jonathan

AU - Chenevix-Trench, Georgia

PY - 2019/4/15

Y1 - 2019/4/15

N2 - 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.

AB - 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.

KW - Cancer

KW - Genetics

KW - Krabbamein

KW - Erfðafræði

KW - Brjóstakrabbamein

KW - Erfðarannsóknir

KW - Gen

KW - Breast Neoplasms

KW - Genome-Wide Association Study

KW - Cancer

KW - Genetics

KW - Krabbamein

KW - Erfðafræði

KW - Brjóstakrabbamein

KW - Erfðarannsóknir

KW - Gen

KW - Breast Neoplasms

KW - Genome-Wide Association Study

U2 - 10.1038/s41467-018-08053-5

DO - 10.1038/s41467-018-08053-5

M3 - Article

C2 - 30988301

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

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