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 journalArticlepeer-review


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 languageEnglish
Pages (from-to)2513-2517
Issue number16
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Hematology


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