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Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in<jats:italic>JAK2<\/jats:italic><jats:sup>V617F<\/jats:sup>-negative MPN: rs12339666 (<jats:italic>JAK2;<\/jats:italic>meta-analysis<jats:italic>P<\/jats:italic>=1.27 \u00d7 10<jats:sup>\u221210<\/jats:sup>) and rs2201862 (<jats:italic>MECOM<\/jats:italic>; meta-analysis<jats:italic>P<\/jats:italic>=1.96 \u00d7 10<jats:sup>\u22129<\/jats:sup>). Two additional SNPs, rs2736100 (<jats:italic>TERT<\/jats:italic>) and rs9376092 (<jats:italic>HBS1L<\/jats:italic>\/<jats:italic>MYB<\/jats:italic>), achieve genome-wide significance when including<jats:italic>JAK2<\/jats:italic><jats:sup>V617F<\/jats:sup>-positive cases. rs9376092 has a stronger effect in<jats:italic>JAK2<\/jats:italic><jats:sup>V617F<\/jats:sup>-negative cases with<jats:italic>CALR<\/jats:italic>and\/or<jats:italic>MPL<\/jats:italic>mutations (Breslow\u2013Day<jats:italic>P<\/jats:italic>=4.5 \u00d7 10<jats:sup>\u22127<\/jats:sup>), whereas in<jats:italic>JAK2<\/jats:italic><jats:sup>V617F<\/jats:sup>-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup><jats:italic>P<\/jats:italic>=7.3 \u00d7 10<jats:sup>\u22127<\/jats:sup>). Reduced<jats:italic>MYB<\/jats:italic>expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in<jats:italic>MYB<\/jats:italic>expression to disease phenotype.<\/jats:p>","DOI":"10.1038\/ncomms7691","type":"journal-article","created":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T13:22:17Z","timestamp":1428412937000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":167,"title":["Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms"],"prefix":"10.1038","volume":"6","author":[{"given":"William","family":"Tapper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy 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