TY - JOUR
T1 - Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
AU - The PRACTICAL Consortium
AU - Went, Molly
AU - Sud, Amit
AU - Försti, Asta
AU - Halvarsson, Britt-marie
AU - Weinhold, Niels
AU - Kimber, Scott
AU - Van Duin, Mark
AU - Thorleifsson, Gudmar
AU - Holroyd, Amy
AU - Johnson, David C.
AU - Li, Ni
AU - Orlando, Giulia
AU - Law, Philip J.
AU - Ali, Mina
AU - Chen, Bowang
AU - Mitchell, Jonathan S.
AU - Gudbjartsson, Daniel F.
AU - Kuiper, Rowan
AU - Stephens, Owen W.
AU - Bertsch, Uta
AU - Broderick, Peter
AU - Campo, Chiara
AU - Bandapalli, Obul R
AU - Einsele, Hermann
AU - Gregory, Walter A.
AU - Gullberg, Urban
AU - Hillengass, Jens
AU - Hoffmann, Per
AU - Jackson, Graham H.
AU - Jöckel, Karl-heinz
AU - Johnsson, Ellinor
AU - Kristinsson, Sigurður Y.
AU - Mellqvist, Ulf-henrik
AU - Nahi, Hareth
AU - Easton, Douglas
AU - Pharoah, Paul
AU - Dunning, Alison
AU - Peto, Julian
AU - Canzian, Federico
AU - Swerdlow, Anthony
AU - Eeles, Rosalind A.
AU - Kote-jarai, Zsofia
AU - Muir, Kenneth
AU - Pashayan, Nora
AU - Nickel, Jolanta
AU - Nöthen, Markus M.
AU - Rafnar, Thorunn
AU - Ross, Fiona M.
AU - Da Silva Filho, Miguel Inacio
AU - Thomsen, Hauke
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-018-04989-w
DO - 10.1038/s41467-018-04989-w
M3 - Article
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -