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 Goldschmidt, Richard S. Houlston () and Gareth J. Morgan
Additional contact information
David C. Johnson: The Institute of Cancer Research
Niels Weinhold: Myeloma Institute, University of Arkansas for Medical Sciences
Jonathan S. Mitchell: The Institute of Cancer Research
Bowang Chen: German Cancer Research Center
Martin Kaiser: The Institute of Cancer Research
Dil B. Begum: The Institute of Cancer Research
Jens Hillengass: University of Heidelberg
Uta Bertsch: University of Heidelberg
Walter A. Gregory: Leeds Institute of Molecular Medicine, Section of Clinical Trials Research, University of Leeds
David Cairns: Leeds Institute of Molecular Medicine, Section of Clinical Trials Research, University of Leeds
Graham H. Jackson: Newcastle University
Asta Försti: German Cancer Research Center
Jolanta Nickel: University of Heidelberg
Per Hoffmann: Institute of Human Genetics, University of Bonn
Markus M. Nöethen: Institute of Human Genetics, University of Bonn
Owen W. Stephens: Myeloma Institute, University of Arkansas for Medical Sciences
Bart Barlogie: Myeloma Institute, University of Arkansas for Medical Sciences
Faith E. Davis: Myeloma Institute, University of Arkansas for Medical Sciences
Kari Hemminki: German Cancer Research Center
Hartmut Goldschmidt: University of Heidelberg
Richard S. Houlston: The Institute of Cancer Research
Gareth J. Morgan: Myeloma Institute, University of Arkansas for Medical Sciences

Nature Communications, 2016, vol. 7, issue 1, 1-7

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10290

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