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. The EFO term multiple myeloma 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

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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