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

David C. Johnson, Niels Weinhold, Jonathan S. Mitchell, Bowang Chen, Martin Kaiser, Dil B. Begum, Jens Hillengass, Uta Bertsch, Walter A. Gregory, David Cairns, Graham H. Jackson, Asta Försti, Jolanta Nickel, Per Hoffmann, Markus M. Nöethen, Owen W. Stephens, Bart Barlogie, Faith E. Davis, Kari Hemminki, Hartmut GoldschmidtRichard S. Houlston, Gareth J. Morgan

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 ∼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 × 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.

Original languageEnglish
Article number10290
JournalNature Communications
Volume7
DOIs
StatePublished - 8 Jan 2016
Externally publishedYes

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