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

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 Kuiper, Owen W. Stephens, Uta Bertsch, Peter Broderick, Chiara Campo, Hermann Einsele, Walter A. Gregory, Urban Gullberg, Marc Henrion, Jens Hillengass, Per Hoffmann, Graham H. Jackson, Ellinor Johnsson, Magnus Jöud, Sigurður Y. Kristinsson, Stig Lenhoff, Oleg Lenive, Ulf-Henrik Mellqvist, Gabriele Migliorini, Hareth Nahi, Sven Nelander, Jolanta Nickel, Markus M. Nöthen, Thorunn Rafnar, Fiona M. Ross, Miguel Inacio da Silva Filho, Bhairavi Swaminathan, Hauke Thomsen, Ingemar Turesson, Annette Vangsted, Ulla Vogel, Anders Waage, Brian A. Walker, Anna-Karin Wihlborg, Annemiek Broyl, Faith E. Davies, Unnur Thorsteinsdottir, Christian Langer, Markus Hansson, Martin Kaiser, Pieter Sonneveld, Kari Stefansson, Gareth J. Morgan, Hartmut Goldschmidt, Kari Hemminki (), Björn Nilsson () and Richard S. Houlston ()
Additional contact information
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
Asta Försti: German Cancer Research Center
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
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
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
Graham H. Jackson: Royal Victoria Infirmary
Ellinor Johnsson: Hematology and Transfusion Medicine
Magnus Jöud: Hematology and Transfusion Medicine
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
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
Christian Langer: University of Ulm
Markus Hansson: Hematology and Transfusion Medicine
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
Kari Hemminki: German Cancer Research Center
Björn Nilsson: Hematology and Transfusion Medicine
Richard S. Houlston: The Institute of Cancer Research

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12050

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