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 Myeloproliferative neoplasms. The EFO term myeloproliferative disorder 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: myeloproliferative disorder

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.05

GENES IN THRESHOLD:

6

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-10-22

SPECIES:

AUTHORS:

W Tapper, AV Jones, R Kralovics, AS Harutyunyan, K Zoi, W Leung, AL Godfrey, P Guglielmelli, A Callaway, D Ward, P Aranaz, HE White, K Waghorn, F Lin, A Chase, EJ Baxter, C Maclean, J Nangalia, E Chen, P Evans, M Short, A Jack, L Wallis, D Oscier, AS Duncombe, A Schuh, AJ Mead, M Griffiths, J Ewing, RE Gale, S Schnittger, T Haferlach, F Stegelmann, K Döhner, H Grallert, K Strauch, T Tanaka, S Bandinelli, A Giannopoulos, L Pieri, C Mannarelli, H Gisslinger, G Barosi, M Cazzola, A Reiter, C Harrison, P Campbell, AR Green, A Vannucchi, NC Cross

TITLE:

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms.

JOURNAL:

Nature communications Apr 2015, Vol 6, pp. 6691

ABSTRACT:

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. 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 JAK2(V617F)-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10(-10)) and rs2201862 (MECOM; meta-analysis P=1.96 × 10(-9)). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2(V617F)-positive cases. rs9376092 has a stronger effect in JAK2(V617F)-negative cases with CALR and/or MPL mutations (Breslow-Day P=4.5 × 10(-7)), whereas in JAK2(V617F)-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ(2) P=7.3 × 10(-7)). Reduced MYB 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 MYB expression to disease phenotype. PUBMED: 25849990
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