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Nat Commun. 2016 Jan 8;7:10290. doi: 10.1038/ncomms10290.

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

Author information

1
Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK.
2
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
3
Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, Germany.
4
Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
5
German Cancer Research Center, 69121 Heidelberg, Germany.
6
Leeds Institute of Molecular Medicine, Section of Clinical Trials Research, University of Leeds, Leeds LS2 9PH, UK.
7
Department of Haematology, Newcastle University, Newcastle-upon-Tyne NE1 7RU, UK.
8
Center for Primary Health Care Research, Lund University, 221 00 Malmö, Sweden.
9
Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany.
10
Division of Medical Genetics, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
11
Department of Genomics, Life &Brain Center, University of Bonn, D-53127 Bonn, Germany.
12
National Center of Tumor Diseases, 69120 Heidelberg, Germany.

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.

PMID:
26743840
PMCID:
PMC4729868
DOI:
10.1038/ncomms10290
[Indexed for MEDLINE]
Free PMC Article

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