Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.
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.
|Year of Publication||
2018 09 13
|PubMed Central ID||
P20 GM125503 / GM / NIGMS NIH HHS / United States
U01 CA188392 / CA / NCI NIH HHS / United States
HHSN268201200008C / HL / NHLBI NIH HHS / United States
U19 CA148537 / CA / NCI NIH HHS / United States
14136 / CRUK_ / Cancer Research UK / United Kingdom
Wellcome Trust / United Kingdom
P01 CA055819 / CA / NCI NIH HHS / United States
HHSN268201200008I / HL / NHLBI NIH HHS / United States