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Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk

Nature Genetics volume 44, pages 58–61 (2012)Cite this article

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Abstract

To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 × 10−9) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 × 10−15). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 × 10−7). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights.

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Figure 1: Regional plots of association results and recombination rates for the 2p23.3, 3p22.1 and 7p15.3 susceptibility loci.

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Acknowledgements

We are grateful to all study participants and investigators at the individual centers for taking part. We are extremely grateful to all investigators who contributed to the generation of this data set. We also thank the staff of the Clinical Trials Research Unit (CTRU), University of Leeds, and the National Cancer Research Institute (NCRI) Haematology Clinical Studies Group. We are grateful to all investigators who contributed to the Colorectal Tumour Gene Identification (CORGI) consortium, from which controls in the replication analysis were drawn. The current study made use of genotyping data on the 1958 Birth Cohort. Genotyping data for control subjects was generated by the Wellcome Trust Sanger Institute. A full list of the investigators who contributed to the generation of the data is available from the WTCCC website (see URLs). The GWAS made use of genotyping data from the population-based HNR study. The HNR study was supported by the Heinz-Nixdorf Foundation. The genotyping of the HNR subjects on Illumina HumanOmni1-Quad BeadChips was financed by the German Centre for Neurodegenerative Disorders (DZNE), Bonn. Myeloma UK provided the main funding for the study. Additional funding was provided by Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund), the Leukaemia Lymphoma Research Fund and the National Health Services (NHS) through the Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital NHS Trust. In Germany, funding was provided to Dietmar-Hopp-Stiftung in Walldorf, the University Hospital Heidelberg and a grant from APO-STS (European Union Health-F4-2007-200767). Additionally, the study was funded by the German Ministry of Education and Science and the German Research Council (DFG; Projects SI 236/8-1, SI236/9-1 and ER 155/6-1).

Author information

Author notes

  1. Peter Broderick, Daniel Chubb, David C Johnson and Niels Weinhold: These authors contributed equally to this work.

  2. Kari Hemminki, Gareth J Morgan and Richard S Houlston: These authors jointly directed this work.

Authors and Affiliations

  1. Division of Genetics and Epidemiology, Molecular and Population Genetics, Institute of Cancer Research, Surrey, UK

    Peter Broderick, Daniel Chubb, Amy Lloyd, Bianca Olver, Yussanne P Ma, Sara E Dobbins & Richard S Houlston

  2. Division of Molecular Pathology, Haemato-Oncology Research Unit, Institute of Cancer Research, Surrey, UK

    David C Johnson, Brian A Walker, Faith E Davies, Gareth J Morgan & Richard S Houlston

  3. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

    Niels Weinhold, Kai Neben & Hartmut Goldschmidt

  4. German Cancer Research Center, Heidelberg, Germany

    Asta Försti & Kari Hemminki

  5. Clinical Trials Research Unit, University of Leeds, Leeds, UK

    Walter A Gregory & J Anthony Child

  6. Cytogenetics Group, Wessex Regional Cytogenetic Laboratory, Salisbury, UK

    Fiona M Ross

  7. Royal Victoria Infirmary, Newcastle upon Tyne, UK

    Graham H Jackson

  8. Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany

    Anna Jauch

  9. Institute of Human Genetics, University of Bonn, Bonn, Germany

    Per Hoffmann, Thomas W Mühleisen & Markus M Nöthen

  10. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

    Markus M Nöthen

  11. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg–Essen, Essen, Germany

    Susanne Moebus

  12. Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, Oxford, UK

    Ian P Tomlinson

  13. National Centre of Tumour Diseases, Heidelberg, Germany

    Hartmut Goldschmidt

  14. Center for Primary Health Care Research, Lund University, Malmo, Sweden

    Kari Hemminki

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  1. Peter Broderick
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Contributions

R.S.H. designed the study. R.S.H. and G.J.M. obtained financial support in the UK, and K.H. and H.G. obtained funding in Germany. D.C. performed the main statistical and bioinformatic analyses, and Y.P.M. and S.E.D. performed additional related analyses. P.B. coordinated laboratory studies. A.L. and B.O. performed genotyping of the UK samples. P.H., T.W.M. and M.M.N. performed and coordinated genotyping of the German controls; K.H. and A.F. coordinated genotyping of the German cases. D.C.J. managed and prepared the Myeloma-VII and Myeloma-IX case study DNA samples. H.G., K.N. and N.W. coordinated and managed the German DNA samples. G.J.M., F.E.D., W.A.G., G.H.J. and J.A.C. ascertained and collected case study samples from the UK Myeloma-VII and Myeloma-IX studies. S.M. obtained and managed the HNR samples. I.P.T. acquired colorectal cancer control samples. B.A.W. performed expression analyses on the UK samples. F.M.R. performed FISH analyses on the UK samples, and A.J. performed these analyses on the German samples. R.S.H. drafted the manuscript, and all authors contributed to the final version.

Corresponding author

Correspondence to Richard S Houlston.

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Broderick, P., Chubb, D., Johnson, D. et al. Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk. Nat Genet 44, 58–61 (2012). https://doi.org/10.1038/ng.993

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