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 S.
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 - Neal, David E.
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85053336514&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-04989-w
DO - 10.1038/s41467-018-04989-w
M3 - Artículo
C2 - 30213928
AN - SCOPUS:85053336514
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3707
ER -