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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/cc886a04-06f4-40bf-9434-4bde251aab7e
- author
- 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
- organization
- publishing date
- 2017
- 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
- pmid:29059683
- wos:000414222900051
- ISSN
- 0028-0836
- DOI
- 10.1038/nature24284
- language
- English
- LU publication?
- yes
- additional info
- Export Date: 20 November 2017
- id
- cc886a04-06f4-40bf-9434-4bde251aab7e
- date added to LUP
- 2017-11-20 14:40:31
- date last changed
- 2022-04-25 03:41:33
@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 < 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}},
keywords = {{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}},
doi = {{10.1038/nature24284}},
volume = {{551}},
year = {{2017}},
}