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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Article number7539
JournalNature Communications
Volume6
DOIs
StatePublished - Jul 22 2015

Fingerprint

genome
Genome-Wide Association Study
Multiple Myeloma
Genes
Survival
Chromosomes
Polymorphism
Alleles
genes
mortality
chromosomes
polymorphism
loci
Single Nucleotide Polymorphism
Meta-Analysis
Gene Expression
Mortality

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients. / 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 B; Dumontet, Charles; Dudziński, Marek; Fejerman, Laura; Greenberg, Alexandra; Huntsman, Scott; Jamroziak, Krzysztof; Jurczyszyn, Artur; Kumar, Shaji K; Atanackovic, Djordje; Glenn, Martha; Cannon-Albright, Lisa A.; Jones, Brandt; Lee, Adam; Marques, Herlander; Martin, Thomas; Martinez-Lopez, Joaquin; Rajkumar, S Vincent; Sainz, Juan; Vangsted, Annette Juul; Wątek, Marzena; Wolf, Jeffrey; Slager, Susan L; Camp, Nicola J.; Canzian, Federico; Vachon, Celine M.

In: Nature Communications, Vol. 6, 7539, 22.07.2015.

Research output: Contribution to journalArticle

Ziv, E, Dean, E, Hu, D, Martino, A, Serie, D, Curtin, K, Campa, D, Aftab, B, Bracci, P, Buda, G, Zhao, Y, Caswell-Jin, J, Diasio, RB, Dumontet, C, Dudziński, M, Fejerman, L, Greenberg, A, Huntsman, S, Jamroziak, K, Jurczyszyn, A, Kumar, SK, Atanackovic, D, Glenn, M, Cannon-Albright, LA, Jones, B, Lee, A, Marques, H, Martin, T, Martinez-Lopez, J, Rajkumar, SV, Sainz, J, Vangsted, AJ, Wątek, M, Wolf, J, Slager, SL, Camp, NJ, Canzian, F & Vachon, CM 2015, 'Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients', Nature Communications, vol. 6, 7539. https://doi.org/10.1038/ncomms8539
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 B ; Dumontet, Charles ; Dudziński, Marek ; Fejerman, Laura ; Greenberg, Alexandra ; Huntsman, Scott ; Jamroziak, Krzysztof ; Jurczyszyn, Artur ; Kumar, Shaji K ; Atanackovic, Djordje ; Glenn, Martha ; Cannon-Albright, Lisa A. ; Jones, Brandt ; Lee, Adam ; Marques, Herlander ; Martin, Thomas ; Martinez-Lopez, Joaquin ; Rajkumar, S Vincent ; Sainz, Juan ; Vangsted, Annette Juul ; Wątek, Marzena ; Wolf, Jeffrey ; Slager, Susan L ; Camp, Nicola J. ; Canzian, Federico ; Vachon, Celine M. / Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients. In: Nature Communications. 2015 ; Vol. 6.
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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.",
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AU - Ziv, Elad

AU - Dean, Eric

AU - Hu, Donglei

AU - Martino, Alessandro

AU - Serie, Daniel

AU - Curtin, Karen

AU - Campa, Daniele

AU - Aftab, Blake

AU - Bracci, Paige

AU - Buda, Gabriele

AU - Zhao, Yi

AU - Caswell-Jin, Jennifer

AU - Diasio, Robert B

AU - Dumontet, Charles

AU - Dudziński, Marek

AU - Fejerman, Laura

AU - Greenberg, Alexandra

AU - Huntsman, Scott

AU - Jamroziak, Krzysztof

AU - Jurczyszyn, Artur

AU - Kumar, Shaji K

AU - Atanackovic, Djordje

AU - Glenn, Martha

AU - Cannon-Albright, Lisa A.

AU - Jones, Brandt

AU - Lee, Adam

AU - Marques, Herlander

AU - Martin, Thomas

AU - Martinez-Lopez, Joaquin

AU - Rajkumar, S Vincent

AU - Sainz, Juan

AU - Vangsted, Annette Juul

AU - Wątek, Marzena

AU - Wolf, Jeffrey

AU - Slager, Susan L

AU - Camp, Nicola J.

AU - Canzian, Federico

AU - Vachon, Celine M

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N2 - 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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