Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.
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Authors
Went, M
Sud, A
Försti, A
Halvarsson, B-M
Weinhold, N
Kimber, S
van Duin, M
Thorleifsson, G
Holroyd, A
Johnson, DC
Li, N
Orlando, G
Law, PJ
Ali, M
Chen, B
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
Jöckel, K-H
Johnsson, E
Kristinsson, SY
Mellqvist, U-H
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
Nöthen, MM
Rafnar, T
Ross, FM
da Silva Filho, MI
Thomsen, H
Turesson, I
Vangsted, A
Andersen, NF
Waage, A
Walker, BA
Wihlborg, A-K
Broyl, A
Davies, FE
Thorsteinsdottir, U
Langer, C
Hansson, M
Goldschmidt, H
Kaiser, M
Sonneveld, P
Stefansson, K
Morgan, GJ
Hemminki, K
Nilsson, B
Houlston, RS
PRACTICAL consortium
Sud, A
Försti, A
Halvarsson, B-M
Weinhold, N
Kimber, S
van Duin, M
Thorleifsson, G
Holroyd, A
Johnson, DC
Li, N
Orlando, G
Law, PJ
Ali, M
Chen, B
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
Jöckel, K-H
Johnsson, E
Kristinsson, SY
Mellqvist, U-H
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
Nöthen, MM
Rafnar, T
Ross, FM
da Silva Filho, MI
Thomsen, H
Turesson, I
Vangsted, A
Andersen, NF
Waage, A
Walker, BA
Wihlborg, A-K
Broyl, A
Davies, FE
Thorsteinsdottir, U
Langer, C
Hansson, M
Goldschmidt, H
Kaiser, M
Sonneveld, P
Stefansson, K
Morgan, GJ
Hemminki, K
Nilsson, B
Houlston, RS
PRACTICAL consortium
Document Type
Journal Article
Date
2018-09-13
Date Accepted
2018-06-06
Abstract
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.
Citation
Nature communications, 2018, 9 (1), pp. 3707 - ?
Source Title
Publisher
ISSN
2041-1723
eISSN
2041-1723
Research Team
Aetiological Epidemiology
Cancer Genomics
Myeloma Group
Oncogenetics
Cancer Genomics
Myeloma Group
Oncogenetics