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

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 (2018) Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology. Blood cancer journal, 9 (1). p. 1. ISSN 2044-5385.

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Official URL: https://www.nature.com/articles/s41408-018-0162-8

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 (R = 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
Subjects: WH Haemic and lymphatic systems. Haematology
Divisions: Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Mr Philip O'Reilly
Date Deposited: 07 Jan 2019 14:36
Last Modified: 07 Jan 2019 14:36
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1808

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