Fig. 3

Odds ratios for the associations between genetically predicted circulating vitamin C and site-specific cancers in the replication datasets. The ORs represent the odds ratios per 1-standardized unit (in SD unit) increase in the genetically predicted plasma vitamin C concentration. The random-effects inverse-variance-weighted method was used as the primary approach, while other methods including MR-Egger, weighted median-based, MR-PRESSO, mode-based, MR-Robust, and MR-RAPS were used as sensitivity analyses. The MR-PRESSO global test and MR-Egger regression were used to detect the pleiotropic effects. Using the MR-Egger regression method, the effect of genetic instruments on the exposure is plotted against its effect on the outcome, and an intercept distinct from the origin provides evidence for pleiotropic effects (MR-Egger regression test: p<0.01). We highlighted the outlier-corrected MR estimates using MR-PRESSO and MR-Robust if the horizontal pleiotropy was present (MR-PRESSO global test: p<0.01). The q values derived from the Cochran’s Q statistics were used to reflect heterogeneity between the SNP-specific estimates, and the weighted median-based results should be highlighted if significant heterogeneity was observed. PRESSO, Pleiotropy Residual Sum and Outlier; MBE, mode-based estimation; RAPS, robust-adjusted profile score; ILCCO, International Lung Cancer Consortium; BCAC, the Breast Cancer Association Consortium; PRACTICAL, the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome