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Inherited genetic susceptibility to monoclonal gammopathy of unknown significance

Weinhold, Niels; Johnson, David C.; Rawstron, Andrew C.; Försti, Asta LU ; Doughty, Chi; Vijayakrishnan, Jayaram; Broderick, Peter; Dahir, Nasrin B.; Begum, Dil B. and Hosking, Fay J., et al. (2014) In Blood 123(16). p.2513-2517
Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is present in similar to 2% of individuals age >50 years. The increased risk of multiple myeloma (MM) in relatives of individuals with MGUS is consistent with MGUS being a marker of inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have recently been shown to influence MM risk. To examine the impact of these 7 SNPs on MGUS, we analyzed two case-control series totaling 492 cases and 7306 controls. Each SNP independently influenced MGUS risk with statistically significant associations (P < .02)... (More)
Monoclonal gammopathy of undetermined significance (MGUS) is present in similar to 2% of individuals age >50 years. The increased risk of multiple myeloma (MM) in relatives of individuals with MGUS is consistent with MGUS being a marker of inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have recently been shown to influence MM risk. To examine the impact of these 7 SNPs on MGUS, we analyzed two case-control series totaling 492 cases and 7306 controls. Each SNP independently influenced MGUS risk with statistically significant associations (P < .02) for rs1052501, rs2285803, rs4487645, and rs4273077. SNP associations were independent, with risk increasing with a larger number of risk alleles carried (per allele odds ratio, 1.18; P < 10(-7)). Collectively these data are consistent with a polygenic model of disease susceptibility to MGUS. (Less)
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type
Contribution to journal
publication status
published
subject
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Blood
volume
123
issue
16
pages
2513 - 2517
publisher
American Society of Hematology
external identifiers
  • wos:000335894500018
  • scopus:84899051598
ISSN
1528-0020
DOI
10.1182/blood-2013-10-532283
language
English
LU publication?
yes
id
e8c81294-7922-455d-b096-d8b0f5a85517 (old id 4470129)
date added to LUP
2014-07-01 07:40:20
date last changed
2017-10-08 03:09:56
@article{e8c81294-7922-455d-b096-d8b0f5a85517,
  abstract     = {Monoclonal gammopathy of undetermined significance (MGUS) is present in similar to 2% of individuals age &gt;50 years. The increased risk of multiple myeloma (MM) in relatives of individuals with MGUS is consistent with MGUS being a marker of inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have recently been shown to influence MM risk. To examine the impact of these 7 SNPs on MGUS, we analyzed two case-control series totaling 492 cases and 7306 controls. Each SNP independently influenced MGUS risk with statistically significant associations (P &lt; .02) for rs1052501, rs2285803, rs4487645, and rs4273077. SNP associations were independent, with risk increasing with a larger number of risk alleles carried (per allele odds ratio, 1.18; P &lt; 10(-7)). Collectively these data are consistent with a polygenic model of disease susceptibility to MGUS.},
  author       = {Weinhold, Niels and Johnson, David C. and Rawstron, Andrew C. and Försti, Asta and Doughty, Chi and Vijayakrishnan, Jayaram and Broderick, Peter and Dahir, Nasrin B. and Begum, Dil B. and Hosking, Fay J. and Yong, Kwee and Walker, Brian A. and Hoffmann, Per and Muehleisen, Thomas W. and Langer, Christian and Doerner, Elisabeth and Joeckel, Karl-Heinz and Eisele, Lewin and Noethen, Markus M. and Hose, Dirk and Davies, Faith E. and Goldschmidt, Hartmut and Morgan, Gareth J. and Hemminki, Kari and Houlston, Richard S.},
  issn         = {1528-0020},
  language     = {eng},
  number       = {16},
  pages        = {2513--2517},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Inherited genetic susceptibility to monoclonal gammopathy of unknown significance},
  url          = {http://dx.doi.org/10.1182/blood-2013-10-532283},
  volume       = {123},
  year         = {2014},
}