Johnson, D. C., Weinhold, N., Mitchell, J., Chen, B., Stephens, O. W., Forsti, A., Nickel, J., Kaiser, M., Gregory, W. A., Cairns, D., Jackson, G. H., Hoffmann, P., Noethen, M. M., Hillengass, J., Bertsch, U., Barlogie, B., Davis, F. E., Hemminki, K., Goldschmidt, H., Houlston, R. S., Morgan, G. J. (2016) Genetic factors influencing the risk of multiple myeloma bone disease. LEUKEMIA, 30 (4). pp. 883-888. ISSN 0887-6924

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Abstract

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.

Item Type:	Article
Authors (ICR Faculty only):	Houlston, Richard
All Authors:	Johnson, D. C., Weinhold, N., Mitchell, J., Chen, B., Stephens, O. W., Forsti, A., Nickel, J., Kaiser, M., Gregory, W. A., Cairns, D., Jackson, G. H., Hoffmann, P., Noethen, M. M., Hillengass, J., Bertsch, U., Barlogie, B., Davis, F. E., Hemminki, K., Goldschmidt, H., Houlston, R. S., Morgan, G. J.
Additional Information:	ISI Document Delivery No.: DJ3RK Times Cited: 0 Cited Reference Count: 48 Johnson, D. C. Weinhold, N. Mitchell, J. Chen, B. Stephens, O. W. Foersti, A. Nickel, J. Kaiser, M. Gregory, W. A. Cairns, D. Jackson, G. H. Hoffmann, P. Noethen, M. M. Hillengass, J. Bertsch, U. Barlogie, B. Davis, F. E. Hemminki, K. Goldschmidt, H. Houlston, R. S. Morgan, G. J. Myeloma UK; Leukaemia Lymphoma Research; Cancer Research UK (Bobby Moore Fund) [C1298/A8362]; NHS via the Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital NHS Trust; National Institutes of Health [P01CA055819]; German Ministry of Education and Science (Cliommics) [01ZX1309B]; German Research Council (DFG) [SI 236/8-1, SI236/9-1, ER 155/6-1] Myeloma UK provided principal funding for this study in the United Kingdom. Additional funding was provided by Leukaemia Lymphoma Research, Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) and the NHS via the Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital NHS Trust. The UAMS GWAS was supported by a grant from the National Institutes of Health (P01CA055819). In Germany, funding was provided to Dietmar-Hopp-Stiftung Walldorf, Deutsche Krebshilfe, the University Hospital Heidelberg and Multiple Myeloma Research Foundation. Additionally, funding from by the German Ministry of Education and Science (Cliommics 01ZX1309B) and the German Research Council (DFG; Project SI 236/8-1, SI236/9-1, ER 155/6-1). We are extremely grateful to all investigators who contributed to the generation of this data set. Finally, we are grateful to all the patients and investigators at the individual centers for their participation. We also thank the staff of the CTRU University of Leeds and the NCRI haematology Clinical Studies Group. 0 NATURE PUBLISHING GROUP LONDON LEUKEMIA
Uncontrolled Keywords:	INTERNATIONAL STAGING SYSTEM GENOME-WIDE ASSOCIATION MINERAL DENSITY PAGETS-DISEASE IN-VITRO OSTEOPROTEGERIN CELL EXPRESSION FRACTURES LOCI
Research teams:	ICR divisions > Genetics and Epidemiology > Molecular & Population Genetics ICR divisions > Molecular Pathology > Molecular & Population Genetics ICR divisions > Molecular Pathology > Myeloma Group
Depositing User:	Barry Jenkins
Date Deposited:	09 May 2016 12:33
Last Modified:	09 May 2016 12:43
URI:	http://publications.icr.ac.uk/id/eprint/15018

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