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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 <jats:italic>ELL2<\/jats:italic> (rs56219066T; odds ratio (OR)=1.25; <jats:italic>P<\/jats:italic>=9.6 \u00d7 10<jats:sup>\u221210<\/jats:sup>). 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 <jats:italic>ELL2<\/jats:italic> 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 (<jats:italic>P<\/jats:italic>=8.6 \u00d7 10<jats:sup>\u22129<\/jats:sup> and <jats:italic>P<\/jats:italic>=6.4 \u00d7 10<jats:sup>\u22123<\/jats:sup>, respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; <jats:italic>P<\/jats:italic>=0.0024).<\/jats:p>","DOI":"10.1038\/ncomms8213","type":"journal-article","created":{"date-parts":[[2015,5,26]],"date-time":"2015-05-26T11:47:34Z","timestamp":1432640854000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Variants in ELL2 influencing immunoglobulin levels associate with multiple 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