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; Hans Christiansen; Bent Ejlertsen; Henrik Flyger; Finn C. Nielsen; Qin Wang; 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, Hans Christiansen, Bent Ejlertsen, Henrik Flyger, Finn C. Nielsen, Qin Wang, ABCTB Investigators, HEBON Investigators, BCFR Investigators, OCGN Investigators, GEMO Study Collaborators, EMBRACE Collaborators, GC-HBOC Study Collaborators

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

32 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Tidsskrift	Genetic Epidemiology
Vol/bind	44
Udgave nummer	5
Sider (fra-til)	442-468
ISSN	0741-0395
DOI	https://doi.org/10.1002/gepi.22288
Status	Udgivet - 2020

Adgang til dokumentet

10.1002/gepi.22288Licens: CC BY

Transcriptome-wide association study of breast cancerrisk by estrogen-receptor statusForlagets udgivne version, 2,48 MBLicens: CC BY

Citationsformater

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

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, Christiansen, H, Ejlertsen, B, Flyger, H, Nielsen, FC, Wang, Q, 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, bind 44, nr. 5, s. 442-468. https://doi.org/10.1002/gepi.22288

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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 Hans Christiansen and Bent Ejlertsen and Henrik Flyger and Nielsen, {Finn C.} and Qin Wang 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",

doi = "10.1002/gepi.22288",

language = "English",

volume = "44",

pages = "442--468",

journal = "Genetic Epidemiology",

issn = "0741-0395",

publisher = "JohnWiley & Sons, Inc.",

number = "5",

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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 - Christiansen, Hans

AU - Ejlertsen, Bent

AU - Flyger, Henrik

AU - Nielsen, Finn C.

AU - Wang, Qin

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

Y1 - 2020

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

U2 - 10.1002/gepi.22288

DO - 10.1002/gepi.22288

M3 - Journal article

C2 - 32115800

AN - SCOPUS:85081379482

SN - 0741-0395

VL - 44

SP - 442

EP - 468

JO - Genetic Epidemiology

JF - Genetic Epidemiology

IS - 5

ER -