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; Celine Vachon

doi:10.1038/ncomms8539

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 JurczyszynShaji 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, Celine Vachon

Experimental and Clinical Pharmacology

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English (US)
Article number	7539
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8539
State	Published - Jul 22 2015

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© 2015 Macmillan Publishers Limited. All rights reserved.

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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, R., Dumontet, C., Dudziński, M., Fejerman, L., Greenberg, A., Huntsman, S., Jamroziak, K., ... Vachon, C. (2015). Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients. Nature communications, 6, Article 7539. https://doi.org/10.1038/ncomms8539

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, R, Dumontet, C, Dudziński, M, Fejerman, L, Greenberg, A, Huntsman, S, Jamroziak, K, Jurczyszyn, A, Kumar, S, Atanackovic, D, Glenn, M, Cannon-Albright, LA, Jones, B, Lee, A, Marques, H, Martin, T, Martinez-Lopez, J, Rajkumar, V, Sainz, J, Vangsted, AJ, Wątek, M, Wolf, J, Slager, S, Camp, NJ, Canzian, F & Vachon, C 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

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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 - Curtin, Karen

AU - Campa, Daniele

AU - Aftab, Blake

AU - Bracci, Paige

AU - Buda, Gabriele

AU - Zhao, Yi

AU - Caswell-Jin, Jennifer

AU - Diasio, Robert

AU - Dumontet, Charles

AU - Dudziński, Marek

AU - Fejerman, Laura

AU - Greenberg, Alexandra

AU - Huntsman, Scott

AU - Jamroziak, Krzysztof

AU - Jurczyszyn, Artur

AU - Kumar, Shaji

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, Vincent

AU - Sainz, Juan

AU - Vangsted, Annette Juul

AU - Wątek, Marzena

AU - Wolf, Jeffrey

AU - Slager, Susan

AU - Camp, Nicola J.

AU - Canzian, Federico

AU - Vachon, Celine

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

Abstract

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