Abstract
Environmental, genetic, and social factors are suggested to jointly influence monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma. Aim of this study was to investigate interactions between MGUS-related genetic variants and socioeconomic position (SEP) indicators education and income on MGUS in a population-based study. Two different MGUS-related genetic risk allele sum scores (GRS) were calculated based on recent genome-wide meta-analyses. Odds Ratios (OR) were estimated in 4329 participants including 238 MGUS cases to assess associations and multiplicative interaction. The relative excess risk due to interaction (RERI) was calculated to assess additive interaction. Both GRSs were associated with MGUS. A multiplicative interaction between one GRS and education was observed with genetic effects of OR 1.34 (95% CI 1.11–1.62) per risk allele in the highest and OR 1.06 (95% CI 0.86–1.31) in the lowest education group. A RERI of 0.10 (95% CI 0.05–0.14) also indicated additive interaction. Further, additive GRS by income interaction (RERI 0.07; 95% CI 0.01–0.13) for the same GRS was also indicated. Results indicate interaction between MGUS-related genetic risk and SEP. Non-genetic MGUS risk factors more common in higher education groups may influence the expression of MGUS-related genetic variants.
Highlights
Environmental, genetic, and social factors are suggested to jointly influence monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma
Single SNP associations showed no genome-wide significance; magnitude and direction of effects were consistent to those reported in the original genome-wide association studies (GWASs) for 9/10 of the G RSMGUS2017-SNPs and 7/10 of the GRSMGUS2019-SNPs (Tables S2–S3)
Both genetic risk allele sum scores (GRS) were associated with Monoclonal gammopathy of undetermined significance (MGUS) risk (GRSMGUS2017: Odds Ratios (OR), 1.08; 95% confidence intervals (95% CI), 1.01–1.15; and GRSMGUS2019: OR, 1.12; 95% CI 1.04–1.20 per additional risk allele; Table 2)
Summary
Environmental, genetic, and social factors are suggested to jointly influence monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma. The relative excess risk due to interaction (RERI) was calculated to assess additive interaction Results indicate interaction between MGUS-related genetic risk and SEP. Several genome-wide association studies (GWASs) have identified multiple risk loci for MGUS and multiple myeloma. Genetic susceptibility of MGUS has only been studied to a limited extent, with two interrelated GWASs each identifying 10 different risk loci with suggestive evidence of genome-wide association[15,17]. Like other polygenetic risk factors for complex disorders, MGUS-related risk alleles only show small to moderate individual effects on the respective outcome One explanation for this are possible gene-environment interactions. Only one population-based study have indicated a positive association between SEP and MGUS while considering other discussed risk factors potentially mediating this effect[23]. Health behaviours, it is hypothesized that SEP may affect disease via its influence on the social distribution of specific risk factors, which in turn have an impact on gene expression (i.e., gene-environment interaction)[24,25]
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