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Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)

Thomsen, Hauke LU ; Campo, Chiara; Weinhold, Niels; da Silva Filho, Miguel Inacio LU ; Pour, Luděk; Gregora, Evžen; Vodicka, Pavel; Vodickova, Ludmila; Hoffmann, Per and Nöthen, Markus M, et al. (2017) In European Journal of Haematology 99(1). p.70-79
Abstract

Objectives: To identify germ line variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant precursor for multiple myeloma (MM). Methods: We conducted the first genomewide association study (GWAS) on MGUS on 243 German cases with a replication on 294 Czech cases. Identified loci were further analyzed in 1508 German MM patients. New MM loci recently reported in a meta-analysis were also tested in the MGUS GWAS. Results: In GWAS, we identified 10 loci contributing to development of MGUS at P-value threshold of 10-5. The Czech cohort gave support for two associations (6q26, rs6933936; 7p21.3 rs10251201). In GWAS, rs974120 (8p23.2) reached genomewide... (More)

Objectives: To identify germ line variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant precursor for multiple myeloma (MM). Methods: We conducted the first genomewide association study (GWAS) on MGUS on 243 German cases with a replication on 294 Czech cases. Identified loci were further analyzed in 1508 German MM patients. New MM loci recently reported in a meta-analysis were also tested in the MGUS GWAS. Results: In GWAS, we identified 10 loci contributing to development of MGUS at P-value threshold of 10-5. The Czech cohort gave support for two associations (6q26, rs6933936; 7p21.3 rs10251201). In GWAS, rs974120 (8p23.2) reached genomewide significance (P=2.94×10-9), with a nominal significance in MM. The locus of rs974120 shows marks of transcriptional activity in leukemia according to ENCODE data. rs10251201 (7p21.3), rs9318227 (13q22.1), and rs10405859 (19q13.32) were associated with markers related to leukemogenesis and immune and inflammatory responses. Two newly identified candidate loci for MM, rs1948915 (8q24.21) and rs8058578 (16p11.2), were nominally associated with MGUS. Conclusions: These data allow a cautious first proposal for a germ line architecture of MGUS with links to leukemia and autoimmune conditions, the latter agreeing with a family study showing clustering of MGUS with autoimmune diseases.

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published
subject
keywords
Germ line, Low-risk genes, Myeloma, Susceptibility
in
European Journal of Haematology
volume
99
issue
1
pages
70 - 79
publisher
Wiley-Blackwell
external identifiers
  • scopus:85019753807
  • wos:000403724300009
ISSN
0902-4441
DOI
10.1111/ejh.12892
language
English
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yes
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f6b45099-47d6-45b2-9497-543a460e1bf6
date added to LUP
2017-06-26 13:50:25
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2017-09-18 11:42:41
@article{f6b45099-47d6-45b2-9497-543a460e1bf6,
  abstract     = {<p>Objectives: To identify germ line variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant precursor for multiple myeloma (MM). Methods: We conducted the first genomewide association study (GWAS) on MGUS on 243 German cases with a replication on 294 Czech cases. Identified loci were further analyzed in 1508 German MM patients. New MM loci recently reported in a meta-analysis were also tested in the MGUS GWAS. Results: In GWAS, we identified 10 loci contributing to development of MGUS at P-value threshold of 10<sup>-5</sup>. The Czech cohort gave support for two associations (6q26, rs6933936; 7p21.3 rs10251201). In GWAS, rs974120 (8p23.2) reached genomewide significance (P=2.94×10<sup>-9</sup>), with a nominal significance in MM. The locus of rs974120 shows marks of transcriptional activity in leukemia according to ENCODE data. rs10251201 (7p21.3), rs9318227 (13q22.1), and rs10405859 (19q13.32) were associated with markers related to leukemogenesis and immune and inflammatory responses. Two newly identified candidate loci for MM, rs1948915 (8q24.21) and rs8058578 (16p11.2), were nominally associated with MGUS. Conclusions: These data allow a cautious first proposal for a germ line architecture of MGUS with links to leukemia and autoimmune conditions, the latter agreeing with a family study showing clustering of MGUS with autoimmune diseases.</p>},
  author       = {Thomsen, Hauke and Campo, Chiara and Weinhold, Niels and da Silva Filho, Miguel Inacio and Pour, Luděk and Gregora, Evžen and Vodicka, Pavel and Vodickova, Ludmila and Hoffmann, Per and Nöthen, Markus M and Jöckel, Karl-Heinz and Langer, Christian and Hajek, Roman and Goldschmidt, Hartmut and Hemminki, Kari and Försti, Asta},
  issn         = {0902-4441},
  keyword      = {Germ line,Low-risk genes,Myeloma,Susceptibility},
  language     = {eng},
  number       = {1},
  pages        = {70--79},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Haematology},
  title        = {Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)},
  url          = {http://dx.doi.org/10.1111/ejh.12892},
  volume       = {99},
  year         = {2017},
}