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; Bent Ejlertsen; Henrik Flyger; Finn C Nielsen; GEMO 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, Bent Ejlertsen, Henrik Flyger, Finn C Nielsen, GEMO Study Collaborators

32 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Genetic Epidemiology
Vol/bind	44
Udgave nummer	5
Sider (fra-til)	442-468
Antal sider	27
ISSN	0741-0395
DOI	https://doi.org/10.1002/gepi.22288
Status	Udgivet - jul. 2020

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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., ... GEMO 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, Campa, D, Carter, BD, Ejlertsen, B , Flyger, H , Nielsen, FC & GEMO 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

@article{0882861fe11249a3af34a899be789e82,

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 Neoplasms/genetics, Estrogens/metabolism, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Receptors, Estrogen/metabolism, Risk Assessment, Transcriptome, Vesicular Transport Proteins/genetics, causal gene, GWAS, breast cancer subtype, 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 Bent Ejlertsen and Henrik Flyger and Nielsen, {Finn C} and {GEMO Study Collaborators}",

note = "{\textcopyright} 2020 The Authors. Genetic Epidemiology published by Wiley Periodicals, Inc.",

year = "2020",

month = jul,

doi = "10.1002/gepi.22288",

language = "English",

volume = "44",

pages = "442--468",

journal = "Genetic Epidemiology",

issn = "0741-0395",

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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 - Ejlertsen, Bent

AU - Flyger, Henrik

AU - Nielsen, Finn C

AU - GEMO 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 Neoplasms/genetics

KW - Estrogens/metabolism

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genomics

KW - Humans

KW - Receptors, Estrogen/metabolism

KW - Risk Assessment

KW - Transcriptome

KW - Vesicular Transport Proteins/genetics

KW - causal gene

KW - GWAS

KW - breast cancer subtype

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 - Journal article

C2 - 32115800

SN - 0741-0395

VL - 44

SP - 442

EP - 468

JO - Genetic Epidemiology

JF - Genetic Epidemiology

IS - 5

ER -

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

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