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Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Went, Molly ; Försti, Asta LU ; Hemminki, Kari LU ; Halvarsson, Britt-Marie LU ; Ali, Mina LU ; Gullberg, Urban LU ; Johnsson, Ellinor LU ; Wihlborg, Anna-Karin LU ; Hansson, Markus LU and Nilsson, Björn LU , et al. (2018) In Nature Communications 9(1).
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... (More)
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. © 2018, The Author(s). (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
9
issue
1
article number
3707
publisher
Nature Publishing Group
external identifiers
  • pmid:30213928
  • scopus:85053336514
ISSN
2041-1723
DOI
10.1038/s41467-018-04989-w
language
English
LU publication?
yes
additional info
Export Date: 8 October 2018
id
8600f211-2e5e-4877-a5bc-4923593e3a18
date added to LUP
2018-10-08 14:21:41
date last changed
2020-10-07 06:04:05
@article{8600f211-2e5e-4877-a5bc-4923593e3a18,
  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. © 2018, The Author(s).},
  author       = {Went, Molly and Försti, Asta and Hemminki, Kari and Halvarsson, Britt-Marie and Ali, Mina and Gullberg, Urban and Johnsson, Ellinor and Wihlborg, Anna-Karin and Hansson, Markus and Nilsson, Björn and Houlston, Richard S},
  issn         = {2041-1723},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma},
  url          = {http://dx.doi.org/10.1038/s41467-018-04989-w},
  doi          = {10.1038/s41467-018-04989-w},
  volume       = {9},
  year         = {2018},
}