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Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients

Author

Listed:
  • Elad Ziv

    (Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California)

  • Eric Dean

    (Sutter Medical Center of Santa Rosa)

  • Donglei Hu

    (Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California)

  • Alessandro Martino

    (Genomic Epidemiology Group, German Cancer Research Center (DKFZ))

  • Daniel Serie

    (Mayo Clinic)

  • Karen Curtin

    (University of Utah School of Medicine)

  • Daniele Campa

    (Genomic Epidemiology Group, German Cancer Research Center (DKFZ))

  • Blake Aftab

    (Helen Diller Family Comprehensive Cancer Center, University of California)

  • Paige Bracci

    (Helen Diller Family Comprehensive Cancer Center, University of California)

  • Gabriele Buda

    (Transplants and Advanced Technologies, Section of Hematology, Pisa University Hospital)

  • Yi Zhao

    (University of Utah School of Medicine)

  • Jennifer Caswell-Jin

    (Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California)

  • Robert Diasio

    (College of Medicine, Mayo Clinic)

  • Charles Dumontet

    (INSERM UMR 1052/CNRS 5286, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, Université Claude Bernard Lyon I)

  • Marek Dudziński

    (Rzeszow Regional Hospital)

  • Laura Fejerman

    (Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California)

  • Alexandra Greenberg

    (Center for Translational Science Activities, Mayo Clinic
    Mayo Clinic)

  • Scott Huntsman

    (Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California)

  • Krzysztof Jamroziak

    (Medical University of Lodz)

  • Artur Jurczyszyn

    (Cracow University Hospital)

  • Shaji Kumar

    (Mayo Clinic)

  • Djordje Atanackovic

    (University of Utah School of Medicine)

  • Martha Glenn

    (University of Utah School of Medicine)

  • Lisa A. Cannon-Albright

    (University of Utah School of Medicine)

  • Brandt Jones

    (University of Utah School of Medicine)

  • Adam Lee

    (College of Medicine, Mayo Clinic)

  • Herlander Marques

    (Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho)

  • Thomas Martin

    (Helen Diller Family Comprehensive Cancer Center, University of California)

  • Joaquin Martinez-Lopez

    (Hematology Service, CRIS facility for Hematological research, Hospital Universitario 12 de Octubre, Universidad Complutense)

  • Vincent Rajkumar

    (Mayo Clinic)

  • Juan Sainz

    (Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government
    Virgen de las Nieves University Hospital)

  • Annette Juul Vangsted

    (Righospitalet and Roskilde Hospital, Copenhagen University)

  • Marzena Wątek

    (Holycross Cancer Center)

  • Jeffrey Wolf

    (Helen Diller Family Comprehensive Cancer Center, University of California)

  • Susan Slager

    (Mayo Clinic College of Medicine)

  • Nicola J. Camp

    (University of Utah School of Medicine)

  • Federico Canzian

    (Genomic Epidemiology Group, German Cancer Research Center (DKFZ))

  • Celine Vachon

    (Mayo Clinic)

Abstract

Here we perform the first genome-wide association study (GWAS) of multiple myeloma (MM) survival. In a meta-analysis of 306 MM patients treated at UCSF and 239 patients treated at the Mayo clinic, we find a significant association between SNPs near the gene FOPNL on chromosome 16p13 and survival (rs72773978; P=6 × 10−10). Patients with the minor allele are at increased risk for mortality (HR: 2.65; 95% CI: 1.94–3.58) relative to patients homozygous for the major allele. We replicate the association in the IMMEnSE cohort including 772 patients, and a University of Utah cohort including 318 patients (rs72773978 P=0.044). Using publicly available data, we find that the minor allele was associated with increased expression of FOPNL and increased expression of FOPNL was associated with higher expression of centrosomal genes and with shorter survival. Polymorphisms at the FOPNL locus are associated with survival among MM patients.

Suggested Citation

  • Elad Ziv & Eric Dean & Donglei Hu & Alessandro Martino & Daniel Serie & Karen Curtin & Daniele Campa & Blake Aftab & Paige Bracci & Gabriele Buda & Yi Zhao & Jennifer Caswell-Jin & Robert Diasio & Cha, 2015. "Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8539
    DOI: 10.1038/ncomms8539
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