Dataset Information

The impact of education inequality on rheumatoid arthritis risk is mediated by smoking and body mass index: Mendelian randomization study.

ABSTRACT:

Objective

To estimate the causal relationship between educational attainment-as a proxy for socioeconomic inequality-and risk of RA, and quantify the roles of smoking and BMI as potential mediators.

Methods

Using the largest genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) study of genetically predicted educational attainment (instrumented using 1265 variants from 766 345 individuals) and RA (14 361 cases, 43 923 controls). We used two-step MR to quantify the proportion of education's effect on RA mediated by smoking exposure (as a composite index capturing duration, heaviness and cessation, using 124 variants from 462 690 individuals) and BMI (517 variants, 681 275 individuals), and multivariable MR to estimate proportion mediated by both factors combined.

Results

Each s.d. increase in educational attainment (4.2 years of schooling) was protective of RA (odds ratio 0.37; 95% CI: 0.31, 0.44). Higher educational attainment was also protective for smoking exposure (β = -0.25 s.d.; 95% CI: -0.26, -0.23) and BMI [β = -0.27 s.d. (∼1.3 kg/m2); 95% CI: -0.31, -0.24]. Smoking mediated 24% (95% CI: 13%, 35%) and BMI 17% (95% CI: 11%, 23%) of the total effect of education on RA. Combined, the two risk factors explained 47% (95% CI: 11%, 82%) of the total effect.

Conclusion

Higher educational attainment has a protective effect on RA risk. Interventions to reduce smoking and excess adiposity at a population level may reduce this risk, but a large proportion of education's effect on RA remains unexplained. Further research into other risk factors that act as potentially modifiable mediators are required.

SUBMITTER: Zhao SS

PROVIDER: S-EPMC9071527 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

The impact of education inequality on rheumatoid arthritis risk is mediated by smoking and body mass index: Mendelian randomization study.

Zhao Sizheng Steven SS Holmes Michael V MV Zheng Jie J Sanderson Eleanor E Carter Alice R AR

Rheumatology (Oxford, England) 20220501 5

<h4>Objective</h4>To estimate the causal relationship between educational attainment-as a proxy for socioeconomic inequality-and risk of RA, and quantify the roles of smoking and BMI as potential mediators.<h4>Methods</h4>Using the largest genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) study of genetically predicted educational attainment (instrumented using 1265 variants from 766 345 individuals) and RA (14 361 cases, 43 923 controls). We used two ...[more]

PMID: 34436562

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Project description:Background: Observational evidence has shown that smoking, alcohol consumption, type 2 diabetes, and body mass index (BMI) are risk factors for peptic ulcer disease (PUD), including gastric ulcer (GU) and duodenal ulcer (DU). However, the observed associations may be confounding factors. Herein, we use Mendelian randomization (MR) to examine causal associations such as smoking, alcohol, type 2 diabetes, BMI, and risks of PUD. Methods: We used 8,17,41,325,82, 231, and 616 identified genetic variants as proxies for age of smoking initiation (AgeSmk), smoking cessation (SmkCes, current/former), number of cigarettes smoked per day (CigDay), smoking status (SmkIni, ever/never), alcohol consumption, type 2 diabetes, and BMI to obtain unconfounded effect estimates on the GU and DU levels among 452,264 participants from the Gene ATLAS. The causal relationship was estimated by using inverse-variance weighted (IVW) as the main method. Sensitivity analysis includes Cochran's Q test, the MR-Egger test, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-robust adjusted profile score (MR-RAPS). In addition, secondary MR analysis was conducted within summary data using genetic risk scores (GRSs) as instrumental variables (IVs). Results: In our two-sample MR analyses, genetic predisposition to smoking (SmkInit) and BMI were associated with an increased risk of GU. The beta values were 0.0035 (95% CI, 0.0021, 0.0049, p = 1.56E-06) for smoking (SmkInit) and 0.0021 (95% CI, 0.0009, 0.0033, p = 0.0008) for BMI. Genetic predisposition to smoking (SmkInit) and higher genetically predicted BMI were associated with an increased risk of DU. The beta values of DU were 0.0029 (95% CI, 0.0017, 0.0041, p = 2.43E-06) for smoking (SmkInit) and 0.0018 (95% CI, 0.0007, 0.0029, p = 0.001) for BMI. No other causal association between smoking (AgeSmk, CigDay, and SmkCes), alcohol consumption, type 2 diabetes, and GU or DU was observed. Consistent results were obtained in sensitivity analyses. Furthermore, the GRS approach showed similar results in the several MR methods. Conclusion: These findings do not support a causal role of AgeSmk, CigDay, SmkCes, alcohol consumption, and type 2 diabetes in the development of GU and DU. However, it is confirmed that SmkInit and BMI have a causal part in the development of GU and DU.

Project description:BackgroundMETARTHROS (Metabolic impact on joint and bone disease) is a nationwide German network to investigate the overlap between inflammatory and metabolic diseases. The objective of this study was to compare the body mass index (BMI) distribution in patients with early and established rheumatoid arthritis (RA) with data from the general population, and to evaluate the association of BMI with patient characteristics and clinical markers.MethodsThe BMI distribution was examined with data collected at inclusion of patients in the early arthritis cohort CAPEA, the biologics register RABBIT, and the National database of the German Collaborative Arthritis Centers. A data source with a representative sample of the German population (German Ageing Survey) was used as a comparator. BMI categories of <18.5 kg/m(2) (underweight), 18.5 to <25 kg/m(2) (normal weight), 25 to <30 kg/m(2) (overweight), and ≥30 kg/m(2) (obese) were used. Patients were stratified by age and sex, and compared to controls from the German Ageing Survey. Associations between BMI and markers of disease activity were analysed with non-parametric tests and linear models.ResultsData from 1207 (CAPEA), 12,230 (RABBIT), and 3424 (National database) RA patients and 6202 population controls were evaluated. The mean age was 56, 56, 62, and 62 years, respectively, the mean disease duration was 13 weeks, 9.9 years, and 13.5 years, respectively, and the mean disease activity score (DAS28) was 5.1, 5.2, and 3.1, respectively. In all RA cohorts, obesity was more frequent (23.8 %, 23.4 %, 21.4 %, respectively) than in controls (18.2 %). This applied to all age groups <70 years, was independent of disease duration, and was more pronounced in females. In all cohorts, the age at RA onset was associated with BMI, being higher in overweight/obese patients compared to normal-weight patients. Current smoking was negatively associated with BMI. Linear analyses revealed increased erythrocyte sedimentation rate (ESR) values in underweight and obese females, and an increasing disparity between tender joint counts (TJCs) and swollen joint counts (SJCs) in higher BMI categories.ConclusionsCompared to the general population, a higher prevalence of obesity was observed in all RA cohorts. The dominance of obesity in females and the different behaviour of disease activity markers in relation to the BMI in females indicate that additional parameters need to be considered when analysing the impact of obesity on inflammation in RA.

Dataset Information

The impact of education inequality on rheumatoid arthritis risk is mediated by smoking and body mass index: Mendelian randomization study.

Objective

Methods

Results

Conclusion

Publications

The impact of education inequality on rheumatoid arthritis risk is mediated by smoking and body mass index: Mendelian randomization study.

Similar Datasets

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