Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.
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Date
2020-07-01Author
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
GEMO Study Collaborators,
EMBRACE Collaborators,
GC-HBOC study Collaborators,
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
ABCTB Investigators,
HEBON Investigators,
BCFR Investigators,
OCGN Investigators,
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, W-Y
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, T-W
Parsons, MT
Pedersen, IS
Peixoto, A
Peterlongo, P
Peto, J
Pharoah, PDP
Phillips, K-A
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, X-O
Simard, J
Singer, CF
Skytte, A-B
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
Kraft, P
Jiang, X
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
GEMO Study Collaborators
EMBRACE Collaborators
GC-HBOC study Collaborators
ABCTB Investigators
HEBON Investigators
BCFR Investigators
OCGN Investigators
Humans
Breast Neoplasms
Genetic Predisposition to Disease
Vesicular Transport Proteins
Receptors, Estrogen
Estrogens
Risk Assessment
Genomics
Female
Genome-Wide Association Study
Transcriptome
Research team
Aetiological Epidemiology
Language
eng
Date accepted
2020-02-13
License start date
2020-07
Citation
Genetic epidemiology, 2020, 44 (5), pp. 442 - 468
Publisher
WILEY
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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