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

Manuel A. Ferreira; Eric R. Gamazon; Fares Al-Ejeh; Kristiina Aittomäki; Irene L. Andrulis; Hoda Anton-Culver; Adalgeir Arason; 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; Julian Adlard; Munaza Ahmed; Julian Barwell; Angela Brady; Carole Brewer; Jackie Cook; Rosemarie Davidson; Alan Donaldson; Jacqueline Eason; Ros Eeles; D. Gareth Evans; Helen Gregory; Helen Hanson; Alex Henderson; Shirley Hodgson; Louise Izatt; M. John Kennedy; Fiona Lalloo; Clare Miller; Patrick J. Morrison; Kai-ren Ong; Jo Perkins; Mary E. Porteous; Mark T. Rogers; Lucy E. 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; Natalie Herold; 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 Sevenet; 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 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; Rosemary Balleine; Robert Baxter; Stephen Braye; Jane Carpenter; Jane Dahlstrom; John Forbes; Soon C. Lee; null et al

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, Eric R. Gamazon, Fares Al-Ejeh, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Adalgeir Arason, 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, Julian Adlard, Munaza Ahmed, Julian Barwell, Angela Brady, Carole Brewer, Jackie Cook, Rosemarie Davidson, Alan Donaldson, Jacqueline Eason, Ros Eeles, D. Gareth Evans, Helen Gregory, Helen Hanson, Alex Henderson, Shirley Hodgson, Louise Izatt, M. John Kennedy, Fiona Lalloo, Clare Miller, Patrick J. Morrison, Kai-ren Ong, Jo Perkins, Mary E. Porteous, Mark T. Rogers, Lucy E. 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, Natalie Herold, 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 Sevenet, 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 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, Rosemary Balleine, Robert Baxter, Stephen Braye, Jane Carpenter, Jane Dahlstrom, John Forbes, Soon C. Lee, et al

Western Sydney University

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

84 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	18
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08053-5
Publication status	Published - 2019

Open Access - Access Right Statement

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Keywords

breast
cancer
gene expression
genes
genomes

UN SDGs

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

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10.1038/s41467-018-08053-5

Cite this

Ferreira, M. A., Gamazon, E. R., Al-Ejeh, F., Aittomäki, K., Andrulis, I. L., Anton-Culver, H., Arason, A., 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., ... et al (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{6f289bec604344a4931d4030866c5b70,

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 = "breast, cancer, gene expression, genes, genomes",

author = "Ferreira, {Manuel A.} and Gamazon, {Eric R.} and Fares Al-Ejeh and Kristiina Aittom{\"a}ki and Andrulis, {Irene L.} and Hoda Anton-Culver and Adalgeir Arason 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 Julian Adlard and Munaza Ahmed and Julian Barwell and Angela Brady and Carole Brewer and Jackie Cook and Rosemarie Davidson and Alan Donaldson and Jacqueline Eason and Ros Eeles and Evans, {D. Gareth} and Helen Gregory and Helen Hanson and Alex Henderson and Shirley Hodgson and Louise Izatt and Kennedy, {M. John} and Fiona Lalloo and Clare Miller and Morrison, {Patrick J.} and Kai-ren Ong and Jo Perkins and Porteous, {Mary E.} and Rogers, {Mark T.} and Side, {Lucy E.} and Katie Snape and Lisa Walker and Harrington, {Patricia A.} and Norbert Arnold and Bernd Auber and Nadja Bogdanova-Markov and Julika Borde and Almuth Caliebe and Nina Ditsch and Bernd Dworniczak and Stefanie Engert and Ulrike Faust and Andrea Gehrig and Eric Hahnen and Jan Hauke and Julia Hentschel and Natalie Herold and Ellen Honisch and Walter Just and Karin Kast and Mirjam Larsen and Johannes Lemke and Nguyen, {Huu Phuc} and Dieter Niederacher and Claus-Eric Ott and Konrad Platzer and Esther Pohl-Rescigno and Juliane Ramser and Kerstin Rhiem and Doris Steinemann and Christian Sutter and Raymonda Varon-Mateeva and Shan Wang-Gohrke and Weber, {Bernhard H. F.} and Fabienne Prieur and Pascal Pujol and Charlotte Sagne and Nicolas Sevenet and Hagay Sobol and Johanna Sokolowska and Dominique Stoppa-Lyonnet and Laurence Venat-Bouvet 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 Rosemary Balleine and Robert Baxter and Stephen Braye and Jane Carpenter and Jane Dahlstrom and John Forbes and Lee, {Soon C.} and {et al}",

year = "2019",

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

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Ferreira, MA, Gamazon, ER, Al-Ejeh, F, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arason, A, 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, Adlard, J, Ahmed, M, Barwell, J, Brady, A, Brewer, C, Cook, J, Davidson, R, Donaldson, A, Eason, J, Eeles, R, Evans, DG, Gregory, H, Hanson, H, Henderson, A, Hodgson, S, Izatt, L, Kennedy, MJ, Lalloo, F, Miller, C, Morrison, PJ, Ong, K, Perkins, J, Porteous, ME, Rogers, MT, Side, LE, Snape, K, Walker, L, Harrington, PA, Arnold, N, Auber, B, Bogdanova-Markov, N, Borde, J, Caliebe, A, Ditsch, N, Dworniczak, B, Engert, S, Faust, U, Gehrig, A, Hahnen, E, Hauke, J, Hentschel, J, Herold, N, Honisch, E, Just, W, Kast, K, Larsen, M, Lemke, J, Nguyen, HP, Niederacher, D, Ott, C-E, Platzer, K, Pohl-Rescigno, E, Ramser, J, Rhiem, K, Steinemann, D, Sutter, C, Varon-Mateeva, R, Wang-Gohrke, S, Weber, BHF, Prieur, F, Pujol, P, Sagne, C, Sevenet, N, Sobol, H, Sokolowska, J, Stoppa-Lyonnet, D, Venat-Bouvet, L, 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, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, SC & et al 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 - Gamazon, Eric R.

AU - Al-Ejeh, Fares

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Arason, Adalgeir

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 - Adlard, Julian

AU - Ahmed, Munaza

AU - Barwell, Julian

AU - Brady, Angela

AU - Brewer, Carole

AU - Cook, Jackie

AU - Davidson, Rosemarie

AU - Donaldson, Alan

AU - Eason, Jacqueline

AU - Eeles, Ros

AU - Evans, D. Gareth

AU - Gregory, Helen

AU - Hanson, Helen

AU - Henderson, Alex

AU - Hodgson, Shirley

AU - Izatt, Louise

AU - Kennedy, M. John

AU - Lalloo, Fiona

AU - Miller, Clare

AU - Morrison, Patrick J.

AU - Ong, Kai-ren

AU - Perkins, Jo

AU - Porteous, Mary E.

AU - Rogers, Mark T.

AU - Side, Lucy E.

AU - Snape, Katie

AU - Walker, Lisa

AU - Harrington, Patricia A.

AU - Arnold, Norbert

AU - Auber, Bernd

AU - Bogdanova-Markov, Nadja

AU - Borde, Julika

AU - Caliebe, Almuth

AU - Ditsch, Nina

AU - Dworniczak, Bernd

AU - Engert, Stefanie

AU - Faust, Ulrike

AU - Gehrig, Andrea

AU - Hahnen, Eric

AU - Hauke, Jan

AU - Hentschel, Julia

AU - Herold, Natalie

AU - Honisch, Ellen

AU - Just, Walter

AU - Kast, Karin

AU - Larsen, Mirjam

AU - Lemke, Johannes

AU - Nguyen, Huu Phuc

AU - Niederacher, Dieter

AU - Ott, Claus-Eric

AU - Platzer, Konrad

AU - Pohl-Rescigno, Esther

AU - Ramser, Juliane

AU - Rhiem, Kerstin

AU - Steinemann, Doris

AU - Sutter, Christian

AU - Varon-Mateeva, Raymonda

AU - Wang-Gohrke, Shan

AU - Weber, Bernhard H. F.

AU - Prieur, Fabienne

AU - Pujol, Pascal

AU - Sagne, Charlotte

AU - Sevenet, Nicolas

AU - Sobol, Hagay

AU - Sokolowska, Johanna

AU - Stoppa-Lyonnet, Dominique

AU - Venat-Bouvet, Laurence

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 - Balleine, Rosemary

AU - Baxter, Robert

AU - Braye, Stephen

AU - Carpenter, Jane

AU - Dahlstrom, Jane

AU - Forbes, John

AU - Lee, Soon C.

AU - et al, null

PY - 2019

Y1 - 2019

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 - breast

KW - cancer

KW - gene expression

KW - genes

KW - genomes

UR - http://handle.westernsydney.edu.au:8081/1959.7/uws:51690

U2 - 10.1038/s41467-018-08053-5

DO - 10.1038/s41467-018-08053-5

M3 - Article

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

Abstract

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Keywords

UN SDGs

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