Non-coding RNAs underlie genetic predisposition to breast cancer

Genetic variants identified through genome-wide association studies (GWAS) are predominantly non-coding and typically attributed to altered regulatory elements such as enhancers and promoters. However, the contribution of non-coding RNAs to complex traits is not clear. Using targeted RNA sequencing,...

Full description

Saved in:
Bibliographic Details
Published in:Genome Biology 2020-01, Vol.21 (1), p.7-7, Article 7
Main Authors: Moradi Marjaneh, Mahdi, Beesley, Jonathan, O'Mara, Tracy A, Mukhopadhyay, Pamela, Koufariotis, Lambros T, Kazakoff, Stephen, Hussein, Nehal, Fachal, Laura, Bartonicek, Nenad, Hillman, Kristine M, Kaufmann, Susanne, Sivakumaran, Haran, Smart, Chanel E, McCart Reed, Amy E, Ferguson, Kaltin, Saunus, Jodi M, Lakhani, Sunil R, Barnes, Daniel R, Antoniou, Antonis C, Dinger, Marcel E, Waddell, Nicola, Easton, Douglas F, Dunning, Alison M, Chenevix-Trench, Georgia, Edwards, Stacey L, French, Juliet D
Format: Article
Language:English
Subjects:
Binding sites
Breast cancer
Breast Neoplasms - genetics
Chromatin
Enhancers
Exons
Gene expression
Gene mapping
Genetic diversity
Genome-wide association studies
Genome-Wide Association Study
Genomes
Humans
Introns
Non-coding RNA
Principal components analysis
Promoters
Proteins
Regulatory sequences
RNA, Untranslated - genetics
Sequence Analysis, RNA
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Genetic variants identified through genome-wide association studies (GWAS) are predominantly non-coding and typically attributed to altered regulatory elements such as enhancers and promoters. However, the contribution of non-coding RNAs to complex traits is not clear. Using targeted RNA sequencing, we systematically annotated multi-exonic non-coding RNA (mencRNA) genes transcribed from 1.5-Mb intervals surrounding 139 breast cancer GWAS signals and assessed their contribution to breast cancer risk. We identify more than 4000 mencRNA genes and show their expression distinguishes normal breast tissue from tumors and different breast cancer subtypes. Importantly, breast cancer risk variants, identified through genetic fine-mapping, are significantly enriched in mencRNA exons, but not the promoters or introns. eQTL analyses identify mencRNAs whose expression is associated with risk variants. Furthermore, chromatin interaction data identify hundreds of mencRNA promoters that loop to regions that contain breast cancer risk variants. We have compiled the largest catalog of breast cancer-associated mencRNAs to date and provide evidence that modulation of mencRNAs by GWAS variants may provide an alternative mechanism underlying complex traits.
ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-019-1876-z