title: Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients.
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.
authors.affiliation: Department of Medicine, Division of General Internal Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.affiliation: Sutter Medical Center of Santa Rosa, Santa Rosa, California.
authors.forename: Eric
authors.initials: E
authors.lastname: Dean
authors.affiliation: Department of Medicine, Division of General Internal Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martino
authors.affiliation: Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Serie
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.affiliation: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
authors.affiliation: Department of Medicine, Division of Hematology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Blake
authors.initials: B
authors.lastname: Aftab
authors.affiliation: Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Paige
authors.initials: P
authors.lastname: Bracci
authors.affiliation: Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University Hospital, Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Buda
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medicine, Division of General Internal Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Caswell-Jin
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Robert
authors.initials: R
authors.lastname: Diasio
authors.affiliation: INSERM UMR 1052 / CNRS 5286, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, Université Claude Bernard Lyon I, Lyon, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.affiliation: Department of Hematology, Rzeszow Regional Hospital, Rzeszow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Dudziński
authors.affiliation: Department of Medicine, Division of General Internal Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Laura
authors.initials: L
authors.lastname: Fejerman
authors.affiliation: Center for Translational Science Activities, Mayo Clinic, Rochester, MN, USA Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Greenberg
authors.affiliation: Department of Medicine, Division of General Internal Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Scott
authors.initials: S
authors.lastname: Huntsman
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jamroziak
authors.affiliation: Department of Hematology, Cracow University Hospital, Cracow, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Jurczyszyn
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Shaji
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Glenn
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Brandt
authors.initials: B
authors.lastname: Jones
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Adam
authors.initials: A
authors.lastname: Lee
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
authors.forename: Herlander
authors.initials: H
authors.lastname: Marques
authors.affiliation: Department of Medicine, Division of Hematology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Thomas
authors.initials: T
authors.lastname: Martin
authors.affiliation: Hematology Service, CRIS facility for Hematological research, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martinez-Lopez
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Rajkumar
authors.affiliation: Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, Granada, Spain; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sainz
authors.affiliation: Department of Hematology, Righospitalet and Roskilde Hospital, Copenhagen University, Denmark.
authors.forename: Annette Juul
authors.initials: AJ
authors.lastname: Vangsted
authors.affiliation: Department of Hematology, Holycross Cancer Center, Kielce, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Wątek
authors.affiliation: Department of Medicine, Division of Hematology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wolf
authors.affiliation: Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Slager
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Camp
authors.affiliation: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine Rochester, MN, USA.
authors.forename: Celine
authors.initials: C
authors.lastname: Vachon
mesh_terms: D002885:Chromosomes, Human, Pair 16; D055106:Genome-Wide Association Study; D006801:Humans; D053208:Kaplan-Meier Estimate; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide