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Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Went, M; Sud, A; Forsti, A; Halvarsson, B-M; Weinhold, N; Kimber, S; van Duin, M; ... The PRACTICAL consortium, .; + view all (2018) Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma. Nature Communications , 9 , Article 3707. 10.1038/s41467-018-04989-w. Green open access

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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.

Type: Article
Title: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-018-04989-w
Publisher version: https://doi.org/10.1038/s41467-018-04989-w
Language: English
Additional information: © The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Applied Health Research
URI: https://discovery.ucl.ac.uk/id/eprint/10057250
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