Genetic factors influencing the risk of multiple myeloma bone disease

D. C. Johnson; N. Weinhold; J. Mitchell; B. Chen; O. W. Stephens; A. Försti; J. Nickel; M. Kaiser; W. A. Gregory; D. Cairns; G. H. Jackson; P. Hoffmann; M. M. Noethen; J. Hillengass; U. Bertsch; B. Barlogie; F. E. Davis; K. Hemminki; H. Goldschmidt; R. S. Houlston; G. J. Morgan

doi:10.1038/leu.2015.342

Genetic factors influencing the risk of multiple myeloma bone disease

D. C. Johnson, N. Weinhold, J. Mitchell, B. Chen, O. W. Stephens, A. Försti, J. Nickel, M. Kaiser, W. A. Gregory, D. Cairns, G. H. Jackson, P. Hoffmann, M. M. Noethen, J. Hillengass, U. Bertsch, B. Barlogie, F. E. Davis, K. Hemminki, H. Goldschmidt, R. S. HoulstonG. J. Morgan

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12 Scopus citations

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 ∼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 × 10 -9) and a promising association at 19q13.43 (rs74676832, odds ratio=1.97, P=9.33 × 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.

Original language	English
Pages (from-to)	883-888
Number of pages	6
Journal	Leukemia
Volume	30
Issue number	4
DOIs	https://doi.org/10.1038/leu.2015.342
State	Published - 1 Apr 2016
Externally published	Yes

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Johnson, D. C., Weinhold, N., Mitchell, J., Chen, B., Stephens, O. W., Försti, 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., ... Morgan, G. J. (2016). Genetic factors influencing the risk of multiple myeloma bone disease. Leukemia, 30(4), 883-888. https://doi.org/10.1038/leu.2015.342

@article{8caa732853974176af63c658153b4131,

title = "Genetic factors influencing the risk of multiple myeloma bone disease",

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 ∼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 × 10 -9) and a promising association at 19q13.43 (rs74676832, odds ratio=1.97, P=9.33 × 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 = "Johnson, {D. C.} and N. Weinhold and J. Mitchell and B. Chen and Stephens, {O. W.} and A. F{\"o}rsti and J. Nickel and M. Kaiser and Gregory, {W. A.} and D. Cairns and Jackson, {G. H.} and P. Hoffmann and Noethen, {M. M.} and J. Hillengass and U. Bertsch and B. Barlogie and Davis, {F. E.} and K. Hemminki and H. Goldschmidt and Houlston, {R. S.} and Morgan, {G. J.}",

note = "Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited.",

year = "2016",

month = apr,

day = "1",

doi = "10.1038/leu.2015.342",

language = "English",

volume = "30",

pages = "883--888",

journal = "Leukemia",

issn = "0887-6924",

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Johnson, DC, Weinhold, N, Mitchell, J, Chen, B, Stephens, OW, Försti, 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 2016, 'Genetic factors influencing the risk of multiple myeloma bone disease', Leukemia, vol. 30, no. 4, pp. 883-888. https://doi.org/10.1038/leu.2015.342

TY - JOUR

T1 - Genetic factors influencing the risk of multiple myeloma bone disease

AU - Johnson, D. C.

AU - Weinhold, N.

AU - Mitchell, J.

AU - Chen, B.

AU - Stephens, O. W.

AU - Försti, A.

AU - Nickel, J.

AU - Kaiser, M.

AU - Gregory, W. A.

AU - Cairns, D.

AU - Jackson, G. H.

AU - Hoffmann, P.

AU - Noethen, M. M.

AU - Hillengass, J.

AU - Bertsch, U.

AU - Barlogie, B.

AU - Davis, F. E.

AU - Hemminki, K.

AU - Goldschmidt, H.

AU - Houlston, R. S.

AU - Morgan, G. J.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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 ∼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 × 10 -9) and a promising association at 19q13.43 (rs74676832, odds ratio=1.97, P=9.33 × 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.

AB - 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 ∼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 × 10 -9) and a promising association at 19q13.43 (rs74676832, odds ratio=1.97, P=9.33 × 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.

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U2 - 10.1038/leu.2015.342

DO - 10.1038/leu.2015.342

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AN - SCOPUS:84954533526

SN - 0887-6924

VL - 30

SP - 883

EP - 888

JO - Leukemia

JF - Leukemia

IS - 4

ER -

Genetic factors influencing the risk of multiple myeloma bone disease

Abstract

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