Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.
View/ Open
Date
2018-09-13ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
PRACTICAL consortium
Chromatin
Humans
Multiple Myeloma
Genetic Predisposition to Disease
Bayes Theorem
Risk
Chromatin Immunoprecipitation
Gene Expression Regulation
Genotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Quality Control
European Continental Ancestry Group
Female
Male
Promoter Regions, Genetic
Genome-Wide Association Study
Research team
Aetiological Epidemiology
Cancer Genomics
Myeloma Group
Oncogenetics
Language
eng
Date accepted
2018-06-06
License start date
2018-09-13
Citation
Nature communications, 2018, 9 (1), pp. 3707 - ?