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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Molly Went
  • Amit Sud
  • Helen Speedy
  • Nicola J. Sunter
  • 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
  • Karin E. Smedby
  • Sandrine Jayne
  • Aneela Majid
  • Claire 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
  • Brian A. Walker
  • Annemiek Broyl
  • Faith E. Davies
  • Hartmut Goldschmidt
  • Martin J.S. Dyer
  • Martin Kaiser
  • Pieter Sonneveld
  • Gareth J. Morgan
  • Daniel Catovsky
  • James M. Allan
  • Richard S. Houlston
Organisations
External organisations
  • Institute of Cancer Research London
  • University of Newcastle upon Tyne
  • German Cancer Research Centre
  • Heidelberg University
  • Erasmus University Medical Center
  • Uppsala University
  • Karolinska Institutet
  • University of Leicester
  • Hull Royal Infirmary
  • Hull York Medical School
  • Birmingham Heartlands Hospital
  • Cardiff University
  • Barts Health NHS Trust
  • Wurzburg University Medical Center
  • University of Leeds
  • University Hospital Bonn
  • University of Basel
  • Royal Victoria Infirmary
  • University Hospital Essen
  • University of Bonn
  • Broad Institute
  • University of Arkansas for Medical Sciences
  • National Centre of Tumor Diseases
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Hematology
Original languageEnglish
Article number1
JournalBlood Cancer Journal
Volume9
Issue number1
Publication statusPublished - 2018 Dec 21
Publication categoryResearch
Peer-reviewedYes

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