medwireNews: Higher educational attainment, as a marker of socioeconomic position, is associated with a lower risk for rheumatoid arthritis (RA), but this protective effect can be moderated by smoking and BMI, suggests an analysis of genetic data.
Alice Carter (University of Bristol, UK) and co-investigators therefore say: “Efforts to reduce smoking and excess adiposity would help mitigate against socioeconomic inequalities in RA.”
Carter and team carried out a Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS) that genetically predicted educational attainment (based on 1265 variants from 766,345 individuals) and RA (14,361 cases, 43,923 controls). They chose educational attainment because it acts “as a good proxy” for socioeconomic position through its strong correlation with employment, income, and other later life measures.
The researchers also used data from GWAS on smoking exposure (124 variants from 462,690 individuals) and BMI (517 variants, 681,275 individuals) to quantify how much of the educational impact on RA is mediated by these variables.
As reported in Rheumatology, each standard deviation (SD) increase in educational attainment, equal to an additional 4.2 years of schooling, was associated with a significant 63% lower risk for RA.
Conversely, each SD increase in smoking exposure was associated with a significant 2.13-fold increased risk for RA, while the risk was increased a significant 1.14-fold with each SD increase in BMI.
Thus, when the impact of smoking and BMI were taken into account, the protective effect of educational attainment was attenuated, with each SD increase now associated with a 41% lower risk for RA.
Carter and colleagues calculated that smoking mediated 24% of the total effect of education on RA and BMI mediated 17% of the effect. Together, the two risk factors accounted for 47% of the impact of education on RA.
This means that “over half of the effect of education remains unaccounted for,” the authors remark.
They note that, in sensitivity analyses, alcohol use, physical activity, and diet were not associated with RA risk, which is in “contrast with a host of observational studies” that do show such associations. They suggest this could be due to unmeasured confounding or the fact that these are difficult to measure in GWAS.
Carter et al conclude: “Further research into other risk factors that act as potentially modifiable mediators are required.”
They add: “Such mediators may be more amenable to intervention, whereas efforts to improve educational opportunities across the population require intervention in early life and are beyond the scope of most clinical practices.”
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Rheumatology 2021; doi:10.1093/rheumatology/keab654