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Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology

Went, Molly ; Sud, Amit ; Speedy, Helen ; Sunter, Nicola J. ; Försti, Asta LU ; Law, Philip J. ; Johnson, David C. ; Mirabella, Fabio ; Holroyd, Amy and Li, Ni , et al. (2018) In Blood Cancer Journal 9(1).
Abstract

The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory... (More)

The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood Cancer Journal
volume
9
issue
1
article number
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85059502420
  • pmid:30602759
ISSN
2044-5385
DOI
10.1038/s41408-018-0162-8
project
Genetic predisposition for multiple myeloma
language
English
LU publication?
yes
id
d988e129-692a-4219-841d-8b4796297a5f
date added to LUP
2019-01-14 12:09:33
date last changed
2023-04-09 01:28:33
@article{d988e129-692a-4219-841d-8b4796297a5f,
  abstract     = {{<p>The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (R<sub>g</sub> = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.</p>}},
  author       = {{Went, Molly and Sud, Amit and Speedy, Helen and Sunter, Nicola J. and Försti, Asta and Law, Philip J. and Johnson, David C. and Mirabella, Fabio and Holroyd, Amy and Li, Ni and Orlando, Giulia and Weinhold, Niels and van Duin, Mark and Chen, Bowang and Mitchell, Jonathan S. and Mansouri, Larry and Juliusson, Gunnar and Smedby, Karin E. and Jayne, Sandrine and Majid, Aneela and Dearden, Claire and Allsup, David J. and Bailey, James R. and Pratt, Guy and Pepper, Chris and Fegan, Chris and Rosenquist, Richard and Kuiper, Rowan and Stephens, Owen W. and Bertsch, Uta and Broderick, Peter and Einsele, Hermann and Gregory, Walter M. and Hillengass, Jens and Hoffmann, Per and Jackson, Graham H. and Jöckel, Karl Heinz and Nickel, Jolanta and Nöthen, Markus M. and da Silva Filho, Miguel Inacio and Thomsen, Hauke and Walker, Brian A. and Broyl, Annemiek and Davies, Faith E. and Hansson, Markus and Goldschmidt, Hartmut and Dyer, Martin J.S. and Kaiser, Martin and Sonneveld, Pieter and Morgan, Gareth J. and Hemminki, Kari and Nilsson, Björn and Catovsky, Daniel and Allan, James M. and Houlston, Richard S.}},
  issn         = {{2044-5385}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Blood Cancer Journal}},
  title        = {{Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology}},
  url          = {{http://dx.doi.org/10.1038/s41408-018-0162-8}},
  doi          = {{10.1038/s41408-018-0162-8}},
  volume       = {{9}},
  year         = {{2018}},
}