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Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Author

Listed:
  • Molly Went

    (The Institute of Cancer Research)

  • Amit Sud

    (The Institute of Cancer Research)

  • Asta Försti

    (German Cancer Research Center
    Lund University)

  • Britt-Marie Halvarsson

    (Lund University)

  • Niels Weinhold

    (University of Arkansas for Medical Sciences
    University of Heidelberg)

  • Scott Kimber

    (The Institute of Cancer Research)

  • Mark Duin

    (Erasmus MC Cancer Institute)

  • Gudmar Thorleifsson

    (deCODE Genetics)

  • Amy Holroyd

    (The Institute of Cancer Research)

  • David C. Johnson

    (The Institute of Cancer Research)

  • Ni Li

    (The Institute of Cancer Research)

  • Giulia Orlando

    (The Institute of Cancer Research)

  • Philip J. Law

    (The Institute of Cancer Research)

  • Mina Ali

    (Lund University)

  • Bowang Chen

    (German Cancer Research Center)

  • Jonathan S. Mitchell

    (The Institute of Cancer Research)

  • Daniel F. Gudbjartsson

    (deCODE Genetics
    University of Iceland)

  • Rowan Kuiper

    (Erasmus MC Cancer Institute)

  • Owen W. Stephens

    (University of Arkansas for Medical Sciences)

  • Uta Bertsch

    (German Cancer Research Center
    National Centre of Tumor Diseases)

  • Peter Broderick

    (The Institute of Cancer Research)

  • Chiara Campo

    (German Cancer Research Center)

  • Obul R Bandapalli

    (German Cancer Research Center)

  • Hermann Einsele

    (University Clinic of Würzburg)

  • Walter A. Gregory

    (University of Leeds)

  • Urban Gullberg

    (Lund University)

  • Jens Hillengass

    (University of Heidelberg)

  • Per Hoffmann

    (University of Bonn
    University of Basel)

  • Graham H. Jackson

    (Royal Victoria Infirmary)

  • Karl-Heinz Jöckel

    (University of Duisburg–Essen)

  • Ellinor Johnsson

    (Lund University)

  • Sigurður Y. Kristinsson

    (National University Hospital of Iceland)

  • Ulf-Henrik Mellqvist

    (Sahlgrenska University Hospital)

  • Hareth Nahi

    (Center for Hematology and Regenerative Medicine)

  • Douglas Easton

    (University of Cambridge
    University of Cambridge)

  • Paul Pharoah

    (University of Cambridge
    University of Cambridge)

  • Alison Dunning

    (University of Cambridge)

  • Julian Peto

    (London School of Hygiene and Tropical Medicine)

  • Federico Canzian

    (German Cancer Research Center (DKFZ))

  • Anthony Swerdlow

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • Rosalind A. Eeles

    (The Institute of Cancer Research
    Royal Marsden NHS Foundation Trust)

  • ZSofia Kote-Jarai

    (The Institute of Cancer Research)

  • Kenneth Muir

    (University of Manchester
    University of Warwick)

  • Nora Pashayan

    (University of Cambridge
    University College London)

  • Jolanta Nickel

    (University of Heidelberg)

  • Markus M. Nöthen

    (University of Bonn
    University of Bonn)

  • Thorunn Rafnar

    (deCODE Genetics)

  • Fiona M. Ross

    (University of Southampton)

  • Miguel Inacio Silva Filho

    (German Cancer Research Center)

  • Hauke Thomsen

    (German Cancer Research Center)

  • Ingemar Turesson

    (Hematology Clinic, Skåne University Hospital)

  • Annette Vangsted

    (University Hospital of Copenhagen at Rigshospitalet)

  • Niels Frost Andersen

    (Aarhus University Hospital)

  • Anders Waage

    (Norwegian University of Science and Technology)

  • Brian A. Walker

    (University of Arkansas for Medical Sciences)

  • Anna-Karin Wihlborg

    (Lund University)

  • Annemiek Broyl

    (Erasmus MC Cancer Institute)

  • Faith E. Davies

    (University of Arkansas for Medical Sciences)

  • Unnur Thorsteinsdottir

    (deCODE Genetics
    University of Iceland)

  • Christian Langer

    (University of Ulm)

  • Markus Hansson

    (Lund University
    Hematology Clinic, Skåne University Hospital)

  • Hartmut Goldschmidt

    (University of Heidelberg
    National Centre of Tumor Diseases)

  • Martin Kaiser

    (The Institute of Cancer Research)

  • Pieter Sonneveld

    (Erasmus MC Cancer Institute)

  • Kari Stefansson

    (deCODE Genetics)

  • Gareth J. Morgan

    (University of Arkansas for Medical Sciences)

  • Kari Hemminki

    (German Cancer Research Center
    Lund University)

  • Björn Nilsson

    (Lund University
    Broad Institute)

  • Richard S. Houlston

    (The Institute of Cancer Research
    The Institute of Cancer Research)

Abstract

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.

Suggested Citation

  • Molly Went & Amit Sud & Asta Försti & Britt-Marie Halvarsson & Niels Weinhold & Scott Kimber & Mark Duin & Gudmar Thorleifsson & Amy Holroyd & David C. Johnson & Ni Li & Giulia Orlando & Philip J. Law, 2018. "Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04989-w
    DOI: 10.1038/s41467-018-04989-w
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    Cited by:

    1. Molly Went & Laura Duran-Lozano & Gisli H. Halldorsson & Andrea Gunnell & Nerea Ugidos-Damboriena & Philip Law & Ludvig Ekdahl & Amit Sud & Gudmar Thorleifsson & Malte Thodberg & Thorunn Olafsdottir &, 2024. "Deciphering the genetics and mechanisms of predisposition to multiple myeloma," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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