DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Multiple myeloma and monoclonal gammopathy. The EFO term multiple myeloma, monoclonal gammopathy was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: multiple myeloma, monoclonal gammopathy

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

B Swaminathan, G Thorleifsson, M Jöud, M Ali, E Johnsson, R Ajore, P Sulem, BM Halvarsson, G Eyjolfsson, V Haraldsdottir, C Hultman, E Ingelsson, SY Kristinsson, AK Kähler, S Lenhoff, G Masson, UH Mellqvist, R Månsson, S Nelander, I Olafsson, O Sigurðardottir, H Steingrimsdóttir, A Vangsted, U Vogel, A Waage, H Nahi, DF Gudbjartsson, T Rafnar, I Turesson, U Gullberg, K Stefánsson, M Hansson, U Thorsteinsdóttir, B Nilsson

TITLE:

Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.

JOURNAL:

Nature communications May 2015, Vol 6, pp. 7213

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). PUBMED: 26007630
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