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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, Law, Philip J., Johnson, David C., Mirabella, Fabio, Holroyd, Amy, Li, Ni, Orlando, Giulia, Weinhold, Niels, van Duin, Mark, Chen, Bowang, Mitchell, Jonathan S., Mansouri, Larry, Juliusson, Gunnar, Smedby, Karin E, Jayne, Sandrine, Majid, Aneela, Dearden, Claire, Allsup, David J., Bailey, James R., Pratt, Guy, Pepper, Chris, Fegan, Chris, Rosenquist, Richard, Kuiper, Rowan, Stephens, Owen W., Bertsch, Uta, Broderick, Peter, Einsele, Hermann, Gregory, Walter M., Hillengass, Jens, Hoffmann, Per, Jackson, Graham H., Jöckel, Karl-Heinz, Nickel, Jolanta, Nöthen, Markus M., da Silva Filho, Miguel Inacio, Thomsen, Hauke, Walker, Brian A., Broyl, Annemiek, Davies, Faith E., Hansson, Markus, Goldschmidt, Hartmut, Dyer, Martin J. S., Kaiser, Martin, Sonneveld, Pieter, Morgan, Gareth J., Hemminki, Kari, Nilsson, Björn, Catovsky, Daniel, Allan, James M. and Houlston, Richard S. 2018. Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology. Blood Cancer Journal 9 (1) , -. 10.1038/s41408-018-0162-8

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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 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

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Springer Nature
ISSN: 2044-5385
Date of First Compliant Deposit: 10 January 2019
Date of Acceptance: 21 December 2018
Last Modified: 28 Feb 2019 22:31
URI: http://orca.cf.ac.uk/id/eprint/118280

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