Skip to main content
. 2023 May 22;92:104620. doi: 10.1016/j.ebiom.2023.104620

Fig. 7.

Fig. 7

Mendelian Randomization (MR) analysis suggests a unidirectional effect of serum triglycerides (TG) on imputed non-alcoholic fatty liver disease (NAFLD) status, mediated by cis regulators of adipose aware DE genes. We derived 6 instrumental variable (IV) variants for MR analysis from the cis regions of adipose aware differentially expressed (DE) genes by selecting adipose cis-expression quantitative trait loci (cis-eQTL) SNPs colocalised with TG GWAS SNPs that were not also NAFLD genome-wide association study (GWAS) SNPs. We then conducted MR analysis with MR-PRESSO using variant GWAS effect sizes from the UK Biobank, and discovered a significant result. (a) Colocalization of VEGFB adipose cis-eQTL rs2845885 with TG GWAS variant rs56271783. Strong colocalization of variants regulating both TGs and adipose expression of an SBC gene suggests that key DE genes and serum TG levels may share a directional pathway. Each point represents one genetic variant, and colour indicates pairwise linkage disequilibrium (LD) with rs56271783, as described in the legend in the left panel. Upper right panel: X-axis represents position on chromosome 11 in megabases (Mb). Y-axis represents the significance of variant association with VEGFB adipose expression, i.e. the negative log p-value from adipose cis-eQTL analysis. Bottom right panel: X-axis represents the position on chromosome 11 in megabases (Mb). Y-axis represents the significance of variant association with serum TG levels, i.e. the negative log P-value from GWAS analysis. Left panel: X-axis represents the negative log p-value from TG GWAS analysis. Y-axis represents the negative log P-value from VEGFB adipose cis-eQTL analysis. Annotation reports the LD value between rs2845885 and rs56271783. (b) Results of MR analysis with MR-PRESSO. The absence of outliers in the plot indicates that there is no significant horizontal pleiotropy in the set of IVs, as evidenced by non-significance in the MR-PRESSO global test. Each point represents an IV, and error bars represent the effect size ± SE. X-axis represents the variant effect size for serum TGs, while Y-axis represents the variant effect size for the imputed NAFLD status. Regression line is generated from the MR-PRESSO output slope with an intercept of 0.