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

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, Charles Dumontet, Marek Dudziński, Laura Fejerman, Alexandra Greenberg, Scott Huntsman, Krzysztof Jamroziak, Artur Jurczyszyn, Shaji Kumar, Djordje Atanackovic, Martha Glenn, Lisa A. Cannon-Albright, Brandt Jones, Adam Lee, Herlander Marques, Thomas Martin, Joaquin Martinez-Lopez, Vincent Rajkumar, Juan Sainz, Annette Juul Vangsted, Marzena Wątek, Jeffrey Wolf, Susan Slager, Nicola J. Camp, Federico Canzian and Celine Vachon
Additional contact information
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
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
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

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8539

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