Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study

Figure 1 Overview of the Mendelian randomization rationale, design, and procedures. GSCAN: Genome-wide association study and Sequencing Consortium of Alcohol and Nicotine Use; GWAS: Genome-wide association study; IVW: Inverse variance weighted; LD: Linkage disequilibrium; MDD: Major depressive disorder; MR: Mendelian randomization; MRC-IEU: The Medical Research Council Integrative Epidemiology Unit; PGC: Psychiatric Genomics Consortium; SNP: Single nucleotide polymorphism; UVMR: Univariate Mendelian randomization.

Figure 2 Forest plots of univariate Mendelian randomization analysis. A: Univariate Mendelian randomization analysis for genetically causal associations of socioeconomic traits with gastroesophageal reflux disease and Barrett’s esophagus risk; B: Forrest plot for causal associations of socioeconomic traits with gastroesophageal reflux diseases and Barrett’s esophagus risk based on inverse variance weighted multivariate Mendelian randomization; C: Mendelian randomization estimates of socioeconomic traits on modifiable risk factors; D: Mendelian randomization estimates of modifiable risk factors on Barrett’s esophagus and gastroesophageal reflux disease. 95%CI: 95% confidence interval; IVW: Inverse variance weighted; SNPs: Single nucleotide polymorphisms.

Figure 3 Mediation effects by multiple mediators on Barrett’s esophagus and gastroesophageal reflux disease. A: Mediation analysis between education attainment and gastroesophageal reflux disease (GERD). The proportion of the effect of educational attainment on GERD was mediated by major depressive disorder (MDD; proportion mediated: 10.83%); B: Mediation analysis between education attainment and Barrett’s esophagus (BE). The effect of educational attainment on BE was mediated by MDD (proportion mediated: 10.58%) and cigarettes smoked per day (proportion mediated: 3.50%); C: Mediation analysis between household income and GERD. Household income had a 9.75% mediating effect on GERD through sleep duration. βa: The effect of socioeconomic status on the risk of modifiable risk factors; βb: The effect of modifiable risk factors on the risk of Barrett’s esophagus and gastroesophageal reflux disease after adjusting socioeconomic status traits. MDD: Major depressive disorder; GRED: Gastroesophageal reflux disease.