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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Went, Molly 
Försti, Asta 
Halvarsson, Britt-Marie 
Weinhold, Niels 

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.

Description

Keywords

Bayes Theorem, Chromatin, Chromatin Immunoprecipitation, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Multiple Myeloma, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Quality Control, Quantitative Trait Loci, Risk, White People

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

9

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research UK (16565)
National Cancer Institute (U19CA148537)
Cancer Research UK (16563)
Cancer Research UK (10118)
Medical Research Council (G1000143)
European Commission (223175)