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Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma

Lookup NU author(s): Professor Graham Jackson


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Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is genotyped for similar to 600,000 single nucleotide polymorphisms across the genome; genotypes for six million common variants are imputed using 1000 Genomes Project and UK10K as the reference. The association between genotype and OS is assessed by Cox proportional hazards model adjusting for age, sex, International staging system and treatment. We identify a locus at 6q25.1 marked by rs12374648 associated with MM-OS (hazard ratio = 1.34, 95% confidence interval = 1.22-1.48, P = 4.69 x 10(-9)). Our findings have potential clinical implications since they demonstrate that inherited genotypes can provide prognostic information in addition to conventional tumor acquired prognostic factors.

Publication metadata

Author(s): Johnson DC, Weinhold N, Mitchell JS, Chen BW, Kaiser M, Begum DB, Hillengass J, Bertsch U, Gregory WA, Cairns D, Jackson GH, Forsti A, Nickel J, Hoffmann P, Noethen MM, Stephens OW, Barlogie B, Davis FE, Hemminki K, Goldschmidt H, Houlston RS, Morgan GJ

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2016

Volume: 7

Issue: 10

Online publication date: 08/01/2016

Acceptance date: 25/11/2015

ISSN (print): 2041-1723

Publisher: Nature Publishing Group


DOI: 10.1038/ncomms10290


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Funder referenceFunder name
Dietmar-Hopp-Stiftung Walldorf
Leukaemia & Lymphoma Research
NHS via the Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital NHS Trust
Deutsche Krebshilfe
German Ministry of Education and Science
University Hospital Heidelberg
C1298/A8362Cancer Research UK - Bobby Moore Fund
DFG CRU 216German Research Council (DFG)
ER 155/6-1German Research Council (DFG)
P01CA055819National Institutes of Health
SI 236/8-1German Research Council (DFG)
SI236/9-1German Research Council (DFG)