期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms8213
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资金
- Swedish Foundation for Strategic Research [KF10-0009]
- Marianne and Marcus Wallenberg Foundation [2010.0112]
- Knut and Alice Wallenberg Foundation [2012.0193]
- Swedish Research Council [2012-1753]
- Royal Swedish Academy of Science
- ALF grants
- Siv-Inger and Per-Erik Andersson Foundation
- Medical Faculty at Lund University
- Swedish Society of Medicine
- Swedish Foundation for Strategic Research (SSF) [KF10-0009] Funding Source: Swedish Foundation for Strategic Research (SSF)
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 x 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 x 10(-9) and P = 6.4 x 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR = 1.30; P = 0.0024).
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