Additional file 2 of The citrate transporter SLC13A5 as a therapeutic target for kidney disease: evidence from Mendelian randomization to inform drug development

Additional file 2: Table S1. Single-nucleotide polymorphisms used as instruments for SLC13A5 inhibition. Genetic associations with plasma citrate are presented for variants within 200kB of the SLC13A5 gene. SNP: single-nucleotide polymorphism. Table S2. Annotation of the functional consequences of the single-nucleotide polymorphisms used to instruments SLC13A5 inhibition using the PhenoScanner version 2 database. Table S3. Associations of the variants employed as instruments for SLC13A5 inhibition in the PhenoScanner version 2 database below the recommended threshold ofP<5x10-5, which accounts for multiple testing of the 1490 included genome-wide association studies. Table S4. Inverse-variance weighted Mendelian randomization sensitivity analyses using a pruning correlation threshold of r2<0.01 for variants employed as instruments. The exposure is genetically proxied SLC13A5 inhibition, as in the main analysis. This sensitivity analysis is performed for the primary outcomes, related to kidney traits. Table S5. Results of the genetic colocalisation analysis. H0 signifies the probability that there is no genetic association in the SLC13A5 gene region with either plasma citrate or the considered outcome. H1 signifies the probability that there is only an association with plasma citrate. H2 signifies the probability that there is only an association with the outcome. H3 signifies the probability that there is an association with plasma citrate and the outcome that is attributable to distinct causal variants. H4 signifies the probability that there is an association with plasma citrate and the outcome that is attributable to a shared causal variant. Table S6. Metabolome-wide Mendelian randomization analysis investigating the associations of genetically proxied SLC13A5 inhibition with plasma metabolites. CI: confidence interval. Table S7. Metabolome-wide Mendelian randomization analysis investigating the associations of genetically proxied SLC13A5 inhibition with urine metabolites. CI: confidence interval. Table S8. Proteome-wide Mendelian randomization analysis investigating the associations of genetically proxied SLC13A5 inhibition with plasma protein-binding aptamers. Table S9. Phenome-wide association study investigating the associations of a standardised genetic risk score for SLC13A5 inhibition with clinical outcomes across the phenome. Table S10. Single-nucleotide polymorphisms used as instruments for plasma citrate levels, selected from throughout the genome. SNP: single-nucleotide polymorphism. Table S11. Metabolome-wide Mendelian randomization analysis investigating the associations of genetically predicted plasma citrate levels with plasma metabolites. CI: confidence interval. Table S12. Metabolome-wide Mendelian randomization analysis investigating the associations of genetically predicted plasma citrate levels with urine metabolites. CI: confidence interval. Table S13. Proteome-wide Mendelian randomization analysis investigating the associations of genetically predicted plasma citrate levels with plasma protein-binding aptamers. Table S14. Phenome-wide association study investigating the associations of a standardised genetic risk score for plasma citrate with clinical outcomes across the phenome. Table S15. Mendelian randomization statistical sensitivity analyses for biomarkers of renal function, glucose and lipid metabolism, and inflammation.