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Association analysis identifies 65 new breast cancer risk loci and predicts target genes

Association analysis identifies 65 new breast cancer risk loci and predicts target genes
Association analysis identifies 65 new breast cancer risk loci and predicts target genes
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 ancestry1. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 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.
0028-0836
92-94
Michailidou, Kyriaki
3998b901-962f-4233-b277-483ca6e195b6
Lindstrom, Sara
09faa195-ac21-41b0-a7be-1af78b7b1e19
Dennis, Joe
bd305c84-d968-4946-b154-a5bedb469210
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
et al.
Michailidou, Kyriaki
3998b901-962f-4233-b277-483ca6e195b6
Lindstrom, Sara
09faa195-ac21-41b0-a7be-1af78b7b1e19
Dennis, Joe
bd305c84-d968-4946-b154-a5bedb469210
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23

Michailidou, Kyriaki, Lindstrom, Sara and Dennis, Joe , et al. (2017) Association analysis identifies 65 new breast cancer risk loci and predicts target genes. Nature, 551 (7678), 92-94. (doi:10.1038/nature24284).

Record type: Article

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 ancestry1. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 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.

Text
Oncoarray_Breast_Overall_Main_Letter9Apr_CIRCULATE - Accepted Manuscript
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More information

Accepted/In Press date: 17 September 2017
e-pub ahead of print date: 23 October 2017
Published date: 2 November 2017

Identifiers

Local EPrints ID: 417368
URI: http://eprints.soton.ac.uk/id/eprint/417368
ISSN: 0028-0836
PURE UUID: 41b5a52f-e5a9-4190-b93b-bf62f09c552a
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 30 Jan 2018 17:30
Last modified: 22 Nov 2021 06:05

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Contributors

Author: Kyriaki Michailidou
Author: Sara Lindstrom
Author: Joe Dennis
Author: Diana Eccles ORCID iD
Corporate Author: et al.

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