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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

Author

Listed:
  • Jonathan S. Mitchell

    (The Institute of Cancer Research)

  • Ni Li

    (The Institute of Cancer Research)

  • Niels Weinhold

    (Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences
    University of Heidelberg)

  • Asta Försti

    (German Cancer Research Center
    Center for Primary Health Care Research, Lund University)

  • Mina Ali

    (Hematology and Transfusion Medicine)

  • Mark van Duin

    (Erasmus MC Cancer Institute)

  • Gudmar Thorleifsson

    (deCODE Genetics)

  • David C. Johnson

    (The Institute of Cancer Research)

  • Bowang Chen

    (German Cancer Research Center)

  • Britt-Marie Halvarsson

    (Hematology and Transfusion Medicine)

  • Daniel F. Gudbjartsson

    (deCODE Genetics
    School of Engineering and Natural Sciences, University of Iceland)

  • Rowan Kuiper

    (Erasmus MC Cancer Institute)

  • Owen W. Stephens

    (Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences)

  • Uta Bertsch

    (University of Heidelberg
    National Centre of Tumor Diseases)

  • Peter Broderick

    (The Institute of Cancer Research)

  • Chiara Campo

    (German Cancer Research Center)

  • Hermann Einsele

    (University Clinic of Würzburg)

  • Walter A. Gregory

    (Clinical Trials Research Unit, University of Leeds)

  • Urban Gullberg

    (Hematology and Transfusion Medicine)

  • Marc Henrion

    (The Institute of Cancer Research)

  • Jens Hillengass

    (University of Heidelberg)

  • Per Hoffmann

    (Institute of Human Genetics, University of Bonn
    University of Basel)

  • Graham H. Jackson

    (Royal Victoria Infirmary)

  • Ellinor Johnsson

    (Hematology and Transfusion Medicine)

  • Magnus Jöud

    (Hematology and Transfusion Medicine
    Clinical Immunology and Transfusion Medicine, Laboratory Medicine, Office of Medical Services)

  • Sigurður Y. Kristinsson

    (Landspitali, National University Hospital of Iceland)

  • Stig Lenhoff

    (Hematology Clinic, Skåne University Hospital)

  • Oleg Lenive

    (The Institute of Cancer Research)

  • Ulf-Henrik Mellqvist

    (Section of Hematology, Sahlgrenska University Hospital)

  • Gabriele Migliorini

    (The Institute of Cancer Research)

  • Hareth Nahi

    (Center for Hematology and Regenerative Medicine, Karolinska Institutet)

  • Sven Nelander

    (Rudbeck Laboratory, Pathology and Genetics, Uppsala University)

  • Jolanta Nickel

    (University of Heidelberg)

  • Markus M. Nöthen

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Thorunn Rafnar

    (deCODE Genetics)

  • Fiona M. Ross

    (Wessex Regional Genetics Laboratory, University of Southampton)

  • Miguel Inacio da Silva Filho

    (German Cancer Research Center)

  • Bhairavi Swaminathan

    (Hematology and Transfusion Medicine)

  • Hauke Thomsen

    (German Cancer Research Center)

  • Ingemar Turesson

    (Hematology Clinic, Skåne University Hospital)

  • Annette Vangsted

    (University Hospital of Copenhagen at Rigshospitalet)

  • Ulla Vogel

    (National Research Centre for the Working Environment)

  • Anders Waage

    (Norwegian University of Science and Technology)

  • Brian A. Walker

    (Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences)

  • Anna-Karin Wihlborg

    (Hematology and Transfusion Medicine)

  • Annemiek Broyl

    (Erasmus MC Cancer Institute)

  • Faith E. Davies

    (Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences)

  • Unnur Thorsteinsdottir

    (deCODE Genetics
    Faculty of Medicine, University of Iceland)

  • Christian Langer

    (University of Ulm)

  • Markus Hansson

    (Hematology and Transfusion Medicine
    Hematology Clinic, Skåne University Hospital)

  • Martin Kaiser

    (The Institute of Cancer Research)

  • Pieter Sonneveld

    (Erasmus MC Cancer Institute)

  • Kari Stefansson

    (deCODE Genetics)

  • Gareth J. Morgan

    (Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences)

  • Hartmut Goldschmidt

    (University of Heidelberg
    National Centre of Tumor Diseases)

  • Kari Hemminki

    (German Cancer Research Center
    Center for Primary Health Care Research, Lund University)

  • Björn Nilsson

    (Hematology and Transfusion Medicine
    Clinical Immunology and Transfusion Medicine, Laboratory Medicine, Office of Medical Services
    Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Richard S. Houlston

    (The Institute of Cancer Research)

Abstract

Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 10−13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.

Suggested Citation

  • Jonathan S. Mitchell & Ni Li & Niels Weinhold & Asta Försti & Mina Ali & Mark van Duin & Gudmar Thorleifsson & David C. Johnson & Bowang Chen & Britt-Marie Halvarsson & Daniel F. Gudbjartsson & Rowan , 2016. "Genome-wide association study identifies multiple susceptibility loci for multiple myeloma," Nature Communications, Nature, vol. 7(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12050
    DOI: 10.1038/ncomms12050
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    Cited by:

    1. Pietro Biroli & Titus Galama & Stephanie von Hinke & Hans van Kippersluis & Cornelius Rietveld & Kevin Thom, 2022. "The Economics and Econometrics of Gene-Environment Interplay," Tinbergen Institute Discussion Papers 22-019/V, Tinbergen Institute.
    2. 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.
    3. Fletcher, Jason, 2023. "Decoupling genetics from attainments: The role of social environments," Economics & Human Biology, Elsevier, vol. 50(C).

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