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Association analysis identifies 65 new breast cancer risk loci

Michailidou, Kyriaki; Lindström, Sara ; Dennis, Joe G.; Beesley, Jonathan; Hui, Shirley ; Kar, Siddhartha; Broberg, Per LU ; Ellberg, Carolina LU ; Krüger, Ute LU and Olsson, Håkan LU (2017) In Nature 551(7678). p.92-94
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. 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... (More)
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. 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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
ancestry, cancer, gene, genetic variation, genome, health risk, heritability, polymorphism, tumor, Europe, Far East
in
Nature
volume
551
issue
7678
pages
3 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85033379332
  • wos:000414222900051
ISSN
0028-0836
DOI
10.1038/nature24284
language
English
LU publication?
yes
id
cc886a04-06f4-40bf-9434-4bde251aab7e
date added to LUP
2017-11-20 14:40:31
date last changed
2018-07-15 04:45:43
@article{cc886a04-06f4-40bf-9434-4bde251aab7e,
  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. We identified 65 new loci that are associated with overall breast cancer risk at P &lt; 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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.},
  author       = {Michailidou, Kyriaki and Lindström, Sara  and Dennis, Joe G. and Beesley, Jonathan and Hui, Shirley  and Kar, Siddhartha and Broberg, Per and Ellberg, Carolina and Krüger, Ute and Olsson, Håkan},
  issn         = {0028-0836},
  keyword      = {ancestry,cancer,gene,genetic variation,genome,health risk,heritability,polymorphism,tumor,Europe,Far East},
  language     = {eng},
  number       = {7678},
  pages        = {92--94},
  publisher    = {Nature Publishing Group},
  series       = {Nature},
  title        = {Association analysis identifies 65 new breast cancer risk loci},
  url          = {http://dx.doi.org/10.1038/nature24284},
  volume       = {551},
  year         = {2017},
}