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Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.

Swaminathan, Bhairavi LU ; Thorleifsson, Guðmar; Jöud, Magnus LU ; Ali, Mina LU ; Johnsson, Ellinor LU ; Ajore, Ram LU ; Sulem, Patrick; Halvarsson, Britt-Marie LU ; Eyjolfsson, Guðmundur and Haraldsdottir, Vilhelmina, et al. (2015) In Nature Communications 6(7213). p.1-8
Abstract
Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent... (More)
Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P=8.6 × 10(-9) and P=6.4 × 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; P=0.0024). (Less)
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Contribution to journal
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Nature Communications
volume
6
issue
7213
pages
1 - 8
publisher
Nature Publishing Group
external identifiers
  • pmid:26007630
  • wos:000355537600004
  • scopus:84930226491
ISSN
2041-1723
DOI
10.1038/ncomms8213
language
English
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yes
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49d76660-acbb-4abb-af14-25044a6ee936 (old id 5442375)
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http://www.ncbi.nlm.nih.gov/pubmed/26007630?dopt=Abstract
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2015-06-05 13:27:50
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2017-10-01 04:00:26
@article{49d76660-acbb-4abb-af14-25044a6ee936,
  abstract     = {Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P=8.6 × 10(-9) and P=6.4 × 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; P=0.0024).},
  author       = {Swaminathan, Bhairavi and Thorleifsson, Guðmar and Jöud, Magnus and Ali, Mina and Johnsson, Ellinor and Ajore, Ram and Sulem, Patrick and Halvarsson, Britt-Marie and Eyjolfsson, Guðmundur and Haraldsdottir, Vilhelmina and Hultman, Christina and Ingelsson, Erik and Kristinsson, Sigurður Y and Kähler, Anna K and Lenhoff, Stig and Masson, Gisli and Mellqvist, Ulf-Henrik and Månsson, Robert and Nelander, Sven and Olafsson, Isleifur and Sigurðardottir, Olof and Steingrimsdóttir, Hlif and Vangsted, Annette and Vogel, Ulla and Waage, Anders and Nahi, Hareth and Gudbjartsson, Daniel F and Rafnar, Thorunn and Turesson, Ingemar and Gullberg, Urban and Stefánsson, Kári and Hansson, Markus and Thorsteinsdóttir, Unnur and Nilsson, Björn},
  issn         = {2041-1723},
  language     = {eng},
  number       = {7213},
  pages        = {1--8},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.},
  url          = {http://dx.doi.org/10.1038/ncomms8213},
  volume       = {6},
  year         = {2015},
}