Genetic factors influencing the risk of multiple myeloma bone disease.

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 (totalling 3774) which had been radiologically surveyed for MBD. Each patient had been genotyped for ~600 000 SNPs with genotypes for six million common variants imputed using 1000Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio [OR]=1.38, P=4.09 × 10(-9)) and a promising association at 19q13.43 (rs74676832, OR=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.Leukemia accepted article preview online, 16 December 2015. doi:10.1038/leu.2015.342.

Weinhold, N (author)
Mitchell, J (author)
Chen, B (author)
Stephens, O W (author)
Försti, AstaLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups(Swepub:lu)med-asf (author)
Nickel, J (author)
Kaiser, M (author)
Gregory, W A (author)
Cairns, D (author)
Jackson, G H (author)
Hoffmann, P (author)
Noethen, M M (author)
Hillengass, J (author)
Bertsch, U (author)
Barlogie, B (author)
Davis, F E (author)
Hemminki, KariLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups(Swepub:lu)med-khk (author)
Goldschmidt, H (author)
Houlston, R S (author)
Morgan, G J (author)
Allmänmedicin och klinisk epidemiologiForskargrupper vid Lunds universitet (creator_code:org_t)

In:Leukemia: Springer Science and Business Media LLC30, s. 883-8881476-55510887-6924

By the author/editor: Johnson, D C; Weinhold, N; Mitchell, J; Chen, B; Stephens, O W; Försti, Asta; show more...; 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, Kari; Goldschmidt, H; Houlston, R S; Morgan, G J; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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