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Lookup NU author(s): Professor Graham Jackson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totaling 3774), which had been radiologically surveyed for MBD. Each patient had been genotyped for similar to 6 00 000 single-nucleotide polymorphisms with genotypes for six million common variants imputed using 1000 Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio = 1.38, P = 4.09 x 10(-9)) and a promising association at 19q13.43 (rs74676832, odds ratio = 1.97, P = 9.33 x 10(-7)). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM.
Author(s): Johnson DC, Weinhold N, Mitchell J, Chen B, Stephens OW, Forsti A, Nickel J, Kaiser M, Gregory WA, Cairns D, Jackson GH, Hoffmann P, Noethen MM, Hillengass J, Bertsch U, Barlogie B, Davis FE, Hemminki K, Goldschmidt H, Houlston RS, Morgan GJ
Publication type: Article
Publication status: Published
Journal: Leukemia
Year: 2016
Volume: 30
Issue: 4
Pages: 883-888
Print publication date: 01/04/2016
Online publication date: 12/01/2016
Acceptance date: 30/11/2015
Date deposited: 14/06/2016
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/leu.2015.342
DOI: 10.1038/leu.2015.342
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