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Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma

Author

Listed:
  • David C. Johnson

    (The Institute of Cancer Research)

  • Niels Weinhold

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

  • Jonathan S. Mitchell

    (The Institute of Cancer Research)

  • Bowang Chen

    (German Cancer Research Center)

  • Martin Kaiser

    (The Institute of Cancer Research)

  • Dil B. Begum

    (The Institute of Cancer Research)

  • Jens Hillengass

    (University of Heidelberg)

  • Uta Bertsch

    (University of Heidelberg)

  • Walter A. Gregory

    (Leeds Institute of Molecular Medicine, Section of Clinical Trials Research, University of Leeds)

  • David Cairns

    (Leeds Institute of Molecular Medicine, Section of Clinical Trials Research, University of Leeds)

  • Graham H. Jackson

    (Newcastle University)

  • Asta Försti

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

  • Jolanta Nickel

    (University of Heidelberg)

  • Per Hoffmann

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

  • Markus M. Nöethen

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

  • Owen W. Stephens

    (Myeloma Institute, University of Arkansas for Medical Sciences)

  • Bart Barlogie

    (Myeloma Institute, University of Arkansas for Medical Sciences)

  • Faith E. Davis

    (Myeloma Institute, University of Arkansas for Medical Sciences)

  • Kari Hemminki

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

  • Hartmut Goldschmidt

    (University of Heidelberg
    National Center of Tumor Diseases)

  • Richard S. Houlston

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

  • Gareth J. Morgan

    (Myeloma Institute, University of Arkansas for Medical Sciences)

Abstract

Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is genotyped for ∼600,000 single nucleotide polymorphisms across the genome; genotypes for six million common variants are imputed using 1000 Genomes Project and UK10K as the reference. The association between genotype and OS is assessed by Cox proportional hazards model adjusting for age, sex, International staging system and treatment. We identify a locus at 6q25.1 marked by rs12374648 associated with MM-OS (hazard ratio=1.34, 95% confidence interval=1.22–1.48, P=4.69 × 10–9). Our findings have potential clinical implications since they demonstrate that inherited genotypes can provide prognostic information in addition to conventional tumor acquired prognostic factors.

Suggested Citation

  • David C. Johnson & Niels Weinhold & Jonathan S. Mitchell & Bowang Chen & Martin Kaiser & Dil B. Begum & Jens Hillengass & Uta Bertsch & Walter A. Gregory & David Cairns & Graham H. Jackson & Asta Förs, 2016. "Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma," Nature Communications, Nature, vol. 7(1), pages 1-7, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10290
    DOI: 10.1038/ncomms10290
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    Cited by:

    1. Rounak Dey & Wei Zhou & Tuomo Kiiskinen & Aki Havulinna & Amanda Elliott & Juha Karjalainen & Mitja Kurki & Ashley Qin & Seunggeun Lee & Aarno Palotie & Benjamin Neale & Mark Daly & Xihong Lin, 2022. "Efficient and accurate frailty model approach for genome-wide survival association analysis in large-scale biobanks," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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