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P., Chang-Claude, Jenny, Hall, Per, Hunter, David J., Milne, Roger L., Garcia-Closas, Montserrat, Schmidt, Marjanka K., Chanock, Stephen J., Dunning, Alison M., Edwards, Stacey L., Bader, Gary D., Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Simard, Jacques, Kraft, Peter ORCID: 0000-0002-4472-8103 and Easton, Douglas F.
(2017).
Association analysis identifies 65 new breast cancer risk loci.
Nature, 551 (7678).
S. 92 - 116.
LONDON:
NATURE PUBLISHING GROUP.
ISSN 1476-4687
Full text not available from this repository.
Abstract
Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry(1). We identified 65 new loci that are associated with overall breast cancer risk at P < 5 x 10(-8). The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
Item Type: |
Journal Article
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Creators: |
Creators | Email | ORCID | ORCID Put Code |
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Michailidou, Kyriaki | UNSPECIFIED | orcid.org/0000-0001-7065-1237 | UNSPECIFIED | Lindstrom, Sara | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dennis, Joe | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Beesley, Jonathan | UNSPECIFIED | orcid.org/0000-0003-1942-325X | UNSPECIFIED | Hui, Shirley | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kar, Siddhartha | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lemacon, Audrey | UNSPECIFIED | orcid.org/0000-0002-1817-7029 | UNSPECIFIED | Soucy, Penny | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Glubb, Dylan | UNSPECIFIED | orcid.org/0000-0002-2184-7708 | UNSPECIFIED | Rostamianfar, Asha | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bolla, Manjeet K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wang, Qin | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Tyrer, Jonathan | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dicks, Ed | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lee, Andrew | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wang, Zhaoming | UNSPECIFIED | orcid.org/0000-0001-7556-3869 | UNSPECIFIED | Allen, Jamie | UNSPECIFIED | orcid.org/0000-0002-8677-2225 | UNSPECIFIED | Keeman, Renske | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Eilber, Ursula | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | French, Juliet D. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Chen, Xiao Qing | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Fachal, Laura | UNSPECIFIED | orcid.org/0000-0002-7256-9752 | UNSPECIFIED | McCue, Karen | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | McCart, Amy E. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Reed, Amy E. 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W. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van der Kolk, Lizet | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van der Luijt, Rob B. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Vincent, Daniel | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Vollenweider, Jason | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Waisfisz, Quinten | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wang-Gohrke, Shan | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Weinberg, Clarice R. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wendt, Camilla | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Whittemore, Alice S. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wildiers, Hans | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Willett, Walter | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Winqvist, Robert | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wolk, Alicja | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wu, Anna H. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Xia, Lucy | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Yamaji, Taiki | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Yang, Xiaohong R. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Yip, Cheng Har | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Yoo, Keun-Young | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Yu, Jyh-Cherng | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Zheng, Wei | UNSPECIFIED | orcid.org/0000-0003-1226-070X | UNSPECIFIED | Zheng, Ying | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Zhu, Bin | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Ziogas, Argyrios | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Ziv, Elad | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lakhani, Sunil R. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Antoniou, Antonis C. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Droit, Arnaud | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Andrulis, Irene L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Amos, Christopher I. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Couch, Fergus J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Pharoah, Paul D. P. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Chang-Claude, Jenny | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hall, Per | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hunter, David J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Milne, Roger L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Garcia-Closas, Montserrat | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Schmidt, Marjanka K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Chanock, Stephen J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dunning, Alison M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Edwards, Stacey L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bader, Gary D. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Chenevix-Trench, Georgia | UNSPECIFIED | orcid.org/0000-0002-1878-2587 | UNSPECIFIED | Simard, Jacques | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kraft, Peter | UNSPECIFIED | orcid.org/0000-0002-4472-8103 | UNSPECIFIED | Easton, Douglas F. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
URN: |
urn:nbn:de:hbz:38-211589 |
DOI: |
10.1038/nature24284 |
Journal or Publication Title: |
Nature |
Volume: |
551 |
Number: |
7678 |
Page Range: |
S. 92 - 116 |
Date: |
2017 |
Publisher: |
NATURE PUBLISHING GROUP |
Place of Publication: |
LONDON |
ISSN: |
1476-4687 |
Language: |
English |
Faculty: |
Unspecified |
Divisions: |
Unspecified |
Subjects: |
no entry |
Uncontrolled Keywords: |
Keywords | Language |
---|
GENOME-WIDE ASSOCIATION; COMPREHENSIVE MOLECULAR PORTRAITS; SUSCEPTIBILITY LOCI; PATHWAY ANALYSIS; PROTEIN; EXPRESSION; MUTATIONS; ARCHITECTURE; ANNOTATION; ENHANCERS | Multiple languages | Multidisciplinary Sciences | Multiple languages |
|
Refereed: |
Yes |
URI: |
http://kups.ub.uni-koeln.de/id/eprint/21158 |
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