Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.
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Date
2019-04-15Author
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
EMBRACE Collaborators,
GC-HBOC Study Collaborators,
GEMO Study Collaborators,
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
ABCTB Investigators,
HEBON Investigators,
BCFR Investigators,
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
EMBRACE Collaborators
GC-HBOC Study Collaborators
GEMO Study Collaborators
ABCTB Investigators
HEBON Investigators
BCFR Investigators
Humans
Breast Neoplasms
Genetic Predisposition to Disease
Gene Expression Profiling
Quantitative Trait Loci
Female
Genome-Wide Association Study
Research team
Functional Genetic Epidemiology
Aetiological Epidemiology
Language
eng
Date accepted
2018-12-14
License start date
2019-04-15
Citation
Nature communications, 2019, 10 (1), pp. 1741 - ?
Publisher
NATURE PORTFOLIO
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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