Author(s):
Ziv, Elad ; Dean, Eric ; Hu, Donglei ; Martino, Alessandro ; Serie, Daniel ; Curtin, Karen ; Campa, Daniele ; Aftab, Blake ; Bracci, Paige ; Buda, Gabriele ; Zhao, Yi ; Caswell-Jin, Jennifer ; Diasio, Robert ; Dumontet, Charles ; Dudziński, Marek ; Fejerman, Laura ; Greenberg, Alexandra ; Huntsman, Scott ; Jamroziak, Krzysztof ; Jurczyszyn, Artur ; Kumar, Shaji ; Atanackovic, Djordje ; Glenn, Martha ; Cannon-Albright, Lisa A ; Jones, Brandt ; Lee, Adam ; Marques, Herlander ; Martin, Thomas ; Martinez-Lopez, Joaquin ; Rajkumar, Vincent ; Sainz, Juan ; Vangsted, Annette Juul ; Wątek, Marzena ; Wolf, Jeffrey ; Slager, Susan ; Camp, Nicola J ; Canzian, Federico ; Vachon, Celine
Date: 2015
Persistent ID: https://hdl.handle.net/1822/62280
Origin: RepositóriUM - Universidade do Minho
Subject(s): Genome-Wide Association Study; Humans; Kaplan-Meier Estimate; Multiple Myeloma; Polymorphism, Single Nucleotide; Chromosomes, Human, Pair 16
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.