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

Johnson, David C; Weinhold, Niels; Mitchell, Jonathan S; Chen, Bowang; Kaiser, Martin; Begum, Dil B; Hillengass, Jens; Bertsch, Uta; Gregory, Walter A and Cairns, David, et al. (2016) In Nature Communications 7.
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... (More)
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. (Less)
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Nature Communications
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7
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Nature Publishing Group
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  • pmid:26743840
  • wos:000369021100007
  • scopus:84954094656
ISSN
2041-1723
DOI
10.1038/ncomms10290
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English
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5cee2449-2fa1-4a33-ae00-a7506be11a75 (old id 8592697)
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2016-02-02 09:29:27
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@article{5cee2449-2fa1-4a33-ae00-a7506be11a75,
  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.},
  articleno    = {10290},
  author       = {Johnson, David C and Weinhold, Niels and Mitchell, Jonathan S and Chen, Bowang and Kaiser, Martin and Begum, Dil B and Hillengass, Jens and Bertsch, Uta and Gregory, Walter A and Cairns, David and Jackson, Graham H and Försti, Asta and Nickel, Jolanta and Hoffmann, Per and Nöethen, Markus M and Stephens, Owen W and Barlogie, Bart and Davis, Faith E and Hemminki, Kari and Goldschmidt, Hartmut and Houlston, Richard S and Morgan, Gareth J},
  issn         = {2041-1723},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma.},
  url          = {http://dx.doi.org/10.1038/ncomms10290},
  volume       = {7},
  year         = {2016},
}