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Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
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The PRACTICAL consortium (Including: Muir, Kenneth (Kenneth R.), Went, Molly, Sud, Amit, Försti, Asta , Halvarsson, Britt-Marie and Weinhold, Niels). (2018) Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma. Nature Communications, 9 . 3707 . doi:10.1038/s41467-018-04989-w ISSN 2041-1723.
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WRAP-identification-multiple-risk-loci-regulatory-Muir-2018.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1120Kb) | Preview |
Official URL: https://doi.org/10.1038/s41467-018-04989-w
Abstract
Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||||||||||||||||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||||||||||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Multiple myeloma -- Genetics, Heredity -- Genetics | ||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nature Communications | ||||||||||||||||||||||||||||||||||||||||||
Publisher: | Nature Publishing Group | ||||||||||||||||||||||||||||||||||||||||||
ISSN: | 2041-1723 | ||||||||||||||||||||||||||||||||||||||||||
Official Date: | 13 September 2018 | ||||||||||||||||||||||||||||||||||||||||||
Dates: |
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Volume: | 9 | ||||||||||||||||||||||||||||||||||||||||||
Article Number: | 3707 | ||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/s41467-018-04989-w | ||||||||||||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 19 September 2018 | ||||||||||||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 20 September 2018 | ||||||||||||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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