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.; Houlston, Richard S.

Abstract

© 2018, The Author(s). 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 g = 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.

Citation

Went, M., Sud, A., Speedy, H., Sunter, N. J., Försti, A., Law, P. J., Johnson, D. C., Mirabella, F., Holroyd, A., Li, N., Orlando, G., Weinhold, N., van Duin, M., Chen, B., Mitchell, J. S., Mansouri, L., Juliusson, G., Smedby, K. E., Jayne, S., Majid, A., …Houlston, R. S. (2019). Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology. Blood Cancer Journal, 9(1), Article 1. https://doi.org/10.1038/s41408-018-0162-8

• Journal Article Type: Article
• Acceptance Date: Nov 19, 2018
• Online Publication Date: Dec 21, 2018
• Publication Date: 2019-01
• Deposit Date: Jan 3, 2019
• Publicly Available Date: Jan 3, 2019
• Journal: Blood Cancer Journal
• Print ISSN: 2044-5385
• Publisher: Nature Research (part of Springer Nature)
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 1
• Article Number: 1
• DOI: https://doi.org/10.1038/s41408-018-0162-8
• Keywords: Oncology; Hematology
• Public URL: https://hull-repository.worktribe.com/output/1204155
• Publisher URL: https://www.nature.com/articles/s41408-018-0162-8
• Contract Date: Jan 3, 2019