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

Molly Went, Amit Sud, Helen Speedy, Nicola J. Sunter, Asta Försti, Philip J. Law, David C. Johnson, Fabio Mirabella, Amy Holroyd, Ni Li, Giulia Orlando, Niels Weinhold, Mark van Duin, Bowang Chen, Jonathan S. Mitchell, Larry Mansouri, Gunnar Juliusson, Karin E. Smedby, Sandrine Jayne, Aneela MajidClaire Dearden, David J. Allsup, James R. Bailey, Guy Pratt, Chris Pepper, Chris Fegan, Richard Rosenquist, Rowan Kuiper, Owen W. Stephens, Uta Bertsch, Peter Broderick, Hermann Einsele, Walter M. Gregory, Jens Hillengass, Per Hoffmann, Graham H. Jackson, Karl-Heinz Jöckel, Jolanta Nickel, Markus M. Nöthen, Miguel Inacio da Silva Filho, Hauke Thomsen, Brian A. Walker, Annemiek Broyl, Faith E. Davies, Markus Hansson, Hartmut Goldschmidt, Martin J. S. Dyer, Martin Kaiser, Pieter Sonneveld, Gareth J. Morgan, Kari Hemminki, Björn Nilsson, Daniel Catovsky, James M. Allan, Richard S. Houlston

Research output: Contribution to journalArticleAcademicpeer-review

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 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.
Original languageEnglish
Article number1
JournalBlood cancer journal
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

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