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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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Abstract

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.

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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

URL: http://dx.doi.org/10.1038/ncomms10290

DOI: 10.1038/ncomms10290

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