Inherited genetic susceptibility to monoclonal gammopathy of unknown significance

Niels Weinhold; David C. Johnson; Andrew C. Rawstron; Asta Försti; Chi Doughty; Jayaram Vijayakrishnan; Peter Broderick; Nasrin B. Dahir; Dil B. Begum; Fay J. Hosking; Kwee Yong; Brian A. Walker; Per Hoffmann; Thomas W. Muehleisen; Christian Langer; Elisabeth Doerner; Karl-Heinz Joeckel; Lewin Eisele; Markus M. Noethen; Dirk Hose; Faith E. Davies; Hartmut Goldschmidt; Gareth J. Morgan; Kari Hemminki; Richard S. Houlston

doi:10.1182/blood-2013-10-532283

Inherited genetic susceptibility to monoclonal gammopathy of unknown significance

Niels Weinhold, David C. Johnson, Andrew C. Rawstron, Asta Försti, Chi Doughty, Jayaram Vijayakrishnan, Peter Broderick, Nasrin B. Dahir, Dil B. Begum, Fay J. Hosking, Kwee Yong, Brian A. Walker, Per Hoffmann, Thomas W. Muehleisen, Christian Langer, Elisabeth Doerner, Karl-Heinz Joeckel, Lewin Eisele, Markus M. Noethen, Dirk HoseFaith E. Davies, Hartmut Goldschmidt, Gareth J. Morgan, Kari Hemminki, Richard S. Houlston

Research output: Contribution to journal › Article › peer-review

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is present in similar to 2% of individuals age >50 years. The increased risk of multiple myeloma (MM) in relatives of individuals with MGUS is consistent with MGUS being a marker of inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have recently been shown to influence MM risk. To examine the impact of these 7 SNPs on MGUS, we analyzed two case-control series totaling 492 cases and 7306 controls. Each SNP independently influenced MGUS risk with statistically significant associations (P < .02) for rs1052501, rs2285803, rs4487645, and rs4273077. SNP associations were independent, with risk increasing with a larger number of risk alleles carried (per allele odds ratio, 1.18; P < 10(-7)). Collectively these data are consistent with a polygenic model of disease susceptibility to MGUS.

Original language	English
Pages (from-to)	2513-2517
Journal	Blood
Volume	123
Issue number	16
DOIs	https://doi.org/10.1182/blood-2013-10-532283
Publication status	Published - 2014

Subject classification (UKÄ)

Hematology

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10.1182/blood-2013-10-532283

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Weinhold, N., Johnson, D. C., Rawstron, A. C., Försti, A., Doughty, C., Vijayakrishnan, J., Broderick, P., Dahir, N. B., Begum, D. B., Hosking, F. J., Yong, K., Walker, B. A., Hoffmann, P., Muehleisen, T. W., Langer, C., Doerner, E., Joeckel, K.-H., Eisele, L., Noethen, M. M., ... Houlston, R. S. (2014). Inherited genetic susceptibility to monoclonal gammopathy of unknown significance. Blood, 123(16), 2513-2517. https://doi.org/10.1182/blood-2013-10-532283

@article{e8c812947922455db096d8b0f5a85517,

title = "Inherited genetic susceptibility to monoclonal gammopathy of unknown significance",

abstract = "Monoclonal gammopathy of undetermined significance (MGUS) is present in similar to 2% of individuals age >50 years. The increased risk of multiple myeloma (MM) in relatives of individuals with MGUS is consistent with MGUS being a marker of inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have recently been shown to influence MM risk. To examine the impact of these 7 SNPs on MGUS, we analyzed two case-control series totaling 492 cases and 7306 controls. Each SNP independently influenced MGUS risk with statistically significant associations (P < .02) for rs1052501, rs2285803, rs4487645, and rs4273077. SNP associations were independent, with risk increasing with a larger number of risk alleles carried (per allele odds ratio, 1.18; P < 10(-7)). Collectively these data are consistent with a polygenic model of disease susceptibility to MGUS.",

author = "Niels Weinhold and Johnson, {David C.} and Rawstron, {Andrew C.} and Asta F{\"o}rsti and Chi Doughty and Jayaram Vijayakrishnan and Peter Broderick and Dahir, {Nasrin B.} and Begum, {Dil B.} and Hosking, {Fay J.} and Kwee Yong and Walker, {Brian A.} and Per Hoffmann and Muehleisen, {Thomas W.} and Christian Langer and Elisabeth Doerner and Karl-Heinz Joeckel and Lewin Eisele and Noethen, {Markus M.} and Dirk Hose and Davies, {Faith E.} and Hartmut Goldschmidt and Morgan, {Gareth J.} and Kari Hemminki and Houlston, {Richard S.}",

year = "2014",

doi = "10.1182/blood-2013-10-532283",

language = "English",

volume = "123",

pages = "2513--2517",

journal = "Blood",

issn = "1528-0020",

publisher = "American Society of Hematology",

number = "16",

}

Weinhold, N, Johnson, DC, Rawstron, AC, Försti, A, Doughty, C, Vijayakrishnan, J, Broderick, P, Dahir, NB, Begum, DB, Hosking, FJ, Yong, K, Walker, BA, Hoffmann, P, Muehleisen, TW, Langer, C, Doerner, E, Joeckel, K-H, Eisele, L, Noethen, MM, Hose, D, Davies, FE, Goldschmidt, H, Morgan, GJ, Hemminki, K & Houlston, RS 2014, 'Inherited genetic susceptibility to monoclonal gammopathy of unknown significance', Blood, vol. 123, no. 16, pp. 2513-2517. https://doi.org/10.1182/blood-2013-10-532283

TY - JOUR

T1 - Inherited genetic susceptibility to monoclonal gammopathy of unknown significance

AU - Weinhold, Niels

AU - Johnson, David C.

AU - Rawstron, Andrew C.

AU - Försti, Asta

AU - Doughty, Chi

AU - Vijayakrishnan, Jayaram

AU - Broderick, Peter

AU - Dahir, Nasrin B.

AU - Begum, Dil B.

AU - Hosking, Fay J.

AU - Yong, Kwee

AU - Walker, Brian A.

AU - Hoffmann, Per

AU - Muehleisen, Thomas W.

AU - Langer, Christian

AU - Doerner, Elisabeth

AU - Joeckel, Karl-Heinz

AU - Eisele, Lewin

AU - Noethen, Markus M.

AU - Hose, Dirk

AU - Davies, Faith E.

AU - Goldschmidt, Hartmut

AU - Morgan, Gareth J.

AU - Hemminki, Kari

AU - Houlston, Richard S.

PY - 2014

Y1 - 2014

N2 - Monoclonal gammopathy of undetermined significance (MGUS) is present in similar to 2% of individuals age >50 years. The increased risk of multiple myeloma (MM) in relatives of individuals with MGUS is consistent with MGUS being a marker of inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have recently been shown to influence MM risk. To examine the impact of these 7 SNPs on MGUS, we analyzed two case-control series totaling 492 cases and 7306 controls. Each SNP independently influenced MGUS risk with statistically significant associations (P < .02) for rs1052501, rs2285803, rs4487645, and rs4273077. SNP associations were independent, with risk increasing with a larger number of risk alleles carried (per allele odds ratio, 1.18; P < 10(-7)). Collectively these data are consistent with a polygenic model of disease susceptibility to MGUS.

AB - Monoclonal gammopathy of undetermined significance (MGUS) is present in similar to 2% of individuals age >50 years. The increased risk of multiple myeloma (MM) in relatives of individuals with MGUS is consistent with MGUS being a marker of inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have recently been shown to influence MM risk. To examine the impact of these 7 SNPs on MGUS, we analyzed two case-control series totaling 492 cases and 7306 controls. Each SNP independently influenced MGUS risk with statistically significant associations (P < .02) for rs1052501, rs2285803, rs4487645, and rs4273077. SNP associations were independent, with risk increasing with a larger number of risk alleles carried (per allele odds ratio, 1.18; P < 10(-7)). Collectively these data are consistent with a polygenic model of disease susceptibility to MGUS.

U2 - 10.1182/blood-2013-10-532283

DO - 10.1182/blood-2013-10-532283

M3 - Article

SN - 1528-0020

VL - 123

SP - 2513

EP - 2517

JO - Blood

JF - Blood

IS - 16

ER -

Inherited genetic susceptibility to monoclonal gammopathy of unknown significance

Abstract

Subject classification (UKÄ)

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