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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.

Original publication

DOI

10.1038/s41467-018-04989-w

Type

Journal article

Journal

Nat Commun

Publication Date

13/09/2018

Volume

9

Keywords

Bayes Theorem, Chromatin, Chromatin Immunoprecipitation, European Continental Ancestry Group, 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