Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8600f211-2e5e-4877-a5bc-4923593e3a18
- author
- author collaboration
- organization
-
- EpiHealth: Epidemiology for Health
- Family Medicine and Clinical Epidemiology (research group)
- Hematogenomics (research group)
- Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Division of Hematology and Transfusion Medicine
- Myeloma research group (research group)
- publishing date
- 2018
- 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
- 2022-05-03 06:27:50
@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}}, }