Article open access publication

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

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 6, 1, 2015

DOI:10.1038/ncomms8539, Dimensions: pub.1032505049, PMC: PMC4656791, PMID: 26198393,

Affiliations

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  1. (1) University of California, San Francisco, grid.266102.1
  2. (2) Sutter Santa Rosa Regional Hospital, grid.430771.6
  3. (3) German Cancer Research Center, grid.7497.d
  4. (4) Mayo Clinic, grid.417467.7
  5. (5) University of Utah, grid.223827.e
  6. (6) Azienda Ospedaliera Universitaria Pisana, grid.144189.1
  7. (7) Mayo Clinic, grid.66875.3a
  8. (8) Claude Bernard University Lyon 1, grid.7849.2
  9. (9) Department of Hematology, Rzeszow Regional Hospital, 35-301, Rzeszow, Poland
  10. (10) Medical University of Lodz, grid.8267.b
  11. (11) Department of Hematology, Cracow University Hospital, 31-501, Cracow, Poland
  12. (12) University of Minho, grid.10328.38
  13. (13) Hematology Service, CRIS facility for Hematological research, Hospital Universitario 12 de Octubre, Universidad Complutense, 28041, Madrid, Spain
  14. (14) Hospital Universitario Virgen de las Nieves, grid.411380.f
  15. (15) Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, grid.470860.d
  16. (16) University of Copenhagen, grid.5254.6, KU
  17. (17) Department of Hematology, Holycross Cancer Center, 24-734, Kielce, Poland

Description

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.

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Times Cited: 21

Field Citation Ratio (FCR): 2.81

Relative Citation ratio (RCR): 0.79

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