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

Nat Commun 2018 09 13;9(1):3707. Epub 2018 Sep 13.

Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.

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.

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http://www.nature.com/articles/s41467-018-04989-w
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http://dx.doi.org/10.1038/s41467-018-04989-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137048PMC

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September 2018
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References

(Supplied by CrossRef)
Article in Eur. J. Cancer
A Altieri et al.
Eur. J. Cancer 2006
Article in Nat. Genet.
P Broderick et al.
Nat. Genet. 2011
Article in Nat. Genet.
D Chubb et al.
Nat. Genet. 2013
Article in Nat. Commun.
JS Mitchell et al.
Nat. Commun. 2016
Article in Nat. Commun.
B Swaminathan et al.
Nat. Commun. 2015
Article in Nat. Genet.
N Weinhold et al.
Nat. Genet. 2013
Article in Sci. Rep.
JS Mitchell et al.
Sci. Rep. 2015
Article in Cancer Epidemiol. Biomark. Prev.
CI Amos et al.
Cancer Epidemiol. Biomark. Prev. 2017
Article in Science
N Risch et al.
Science 1996
Article in Am. J. Hum. Genet.
J Wakefield et al.
Am. J. Hum. Genet. 2007
Article in Blood
SW Erickson et al.
Blood 2014

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