Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma.
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Embargo End Date
ICR Authors
Authors
Chattopadhyay, S
Thomsen, H
Yadav, P
da Silva Filho, MI
Weinhold, N
Nöthen, MM
Hoffman, P
Bertsch, U
Huhn, S
Morgan, GJ
Goldschmidt, H
Houlston, R
Hemminki, K
Försti, A
Thomsen, H
Yadav, P
da Silva Filho, MI
Weinhold, N
Nöthen, MM
Hoffman, P
Bertsch, U
Huhn, S
Morgan, GJ
Goldschmidt, H
Houlston, R
Hemminki, K
Försti, A
Document Type
Journal Article
Date
2019-03-04
Date Accepted
2019-01-29
Abstract
Inherited genetic susceptibility to multiple myeloma has been investigated in a number of studies. Although 23 individual risk loci have been identified, much of the genetic heritability remains unknown. Here we carried out genome-wide interaction analyses on two European cohorts accounting for 3,999 cases and 7,266 controls and characterized genetic susceptibility to multiple myeloma with subsequent meta-analysis that discovered 16 unique interacting loci. These risk loci along with previously known variants explain 17% of the heritability in liability scale. The genes associated with the interacting loci were found to be enriched in transforming growth factor beta signaling and circadian rhythm regulation pathways suggesting immunoglobulin trait modulation, TH17 cell differentiation and bone morphogenesis as mechanistic links between the predisposition markers and intrinsic multiple myeloma biology. Further tissue/cell-type enrichment analysis associated the discovered genes with hemic-immune system tissue types and immune-related cell types indicating overall involvement in immune response.
Citation
Communications biology, 2019, 2 pp. 89 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2399-3642
eISSN
2399-3642
Collections
Research Team
Cancer Genomics