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

Went, Molly; Li, Ni; Orlando, Giulia; Weinhold, Niels; van Duin, Mark; Chen, Bowang; Mitchell, Jonathan S.; Mansouri, Larry; Juliusson, Gunnar; Smedby, Karin E; Jayne, Sandrine; Sud, Amit; Majid, Aneela; Dearden, Claire; Allsup, David J.; Bailey, James R.; Pratt, Guy; Pepper, Chris; Fegan, Chris; Rosenquist, Richard; Kuiper, Rowan; Stephens, Owen W.; Speedy, Helen; Bertsch, Uta; Broderick, Peter; Einsele, Hermann; Gregory, Walter M.; Hillengass, Jens; Hoffmann, Per; Jackson, Graham H.; Jöckel, Karl-Heinz; Nickel, Jolanta; Nöthen, Markus M.; Sunter, Nicola J.; 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; Försti, Asta; Morgan, Gareth J.; Hemminki, Kari; Nilsson, Björn; Catovsky, Daniel; Allan, James M.; Houlston, Richard S.; Law, Philip J.; Johnson, David C.; Mirabella, Fabio; Holroyd, Amy

Authors

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 Majid

Claire Dearden

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Dr David Allsup D.J.Allsup@hull.ac.uk
Senior Lecturer in Haematology and Honorary Consultant

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

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

Journal Article Type Article
Publication Date 2019-01
Journal Blood Cancer Journal
Print ISSN 2044-5385
Publisher Springer Nature [academic journals on nature.com]
Peer Reviewed Peer Reviewed
Volume 9
Issue 1
Article Number 1
Institution Citation Went, M., Sud, A., Speedy, H., Sunter, N. J., Försti, A., Law, P. J., …Houlston, R. S. (2019). Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology. Blood Cancer Journal, 9(1), doi:10.1038/s41408-018-0162-8
DOI https://doi.org/10.1038/s41408-018-0162-8
Keywords Oncology; Hematology
Publisher URL https://www.nature.com/articles/s41408-018-0162-8

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