Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
: Went M, Sud A, Forsti A, Halvarsson BM, Weinhold N, Kimber S, van Duin M, Thorleifsson G, Holroydl A, Johnson DC, Li N, Orlando G, Law PJ, Ali M, Chen BW, Mitchell JS, Gudbjartsson DF, Kuiper R, Stephens OW, Bertsch U, Broderick P, Campo C, Bandapalli OR, Einsele H, Gregory WA, Gullberg U, Hillengass J, Hoffmann P, Jackson GH, Jockel KH, Johnsson E, Kristinsson SY, Mellqvist UH, Nahi H, Easton D, Pharoah P, Dunning A, Peto J, Canzian F, Swerdlow A, Eeles RA, Kote-Jarai Z, Muir K, Pashayan N, Nickel J, Nothen MM, Rafnar T, Ross FM, Filho MID, Thomsen H, Turesson I, Vangsted A, Andersen NF, Waage A, Walker BA, Wihlborg AK, Broyl A, Davies FE, Thorsteinsdottir U, Langer C, Hansson M, Goldschmidt H, Kaiser M, Sonneveld P, Stefansson K, Morgans GJ, Hemminki K, Nilsson B, Houlston RS, Nilsson B, Houlston RS; Group Author(s): PRACTICAL Consortium
Publisher: NATURE PUBLISHING GROUP
: 2018
: Nature Communications
: NATURE COMMUNICATIONS
: NAT COMMUN
: ARTN 3707
: 9
: 10
: 2041-1723
: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-04989-w
: https://research.utu.fi/converis/portal/detail/Publication/36105245
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.
