other risk factors as illustrated in Supplementary Fig. 13. It is difficult to distinguish whether the effects of HDL-c on the diseases are mediated or driven by the covariates (Supplementary Fig. 16) because of the complicated association network among risk factors and diseases (Supplementary Fig. 14). Nevertheless, there might be an exception, that is, the association between HDL-c and AMD, because HDL-c is the only risk that showed a significant effect on AMD (OR = 1.36 with PGSMR = 5.9 × 10−16) and the effect size remained largely unchanged and highly significant conditioning on the covariates (conditional OR = 1.36 with PGSMR = 5.1 × 10−13). We conclude that HDL-c is likely to be a direct risk factor for AMD and the effect size is independent of the covariate risk factors analyzed in this study.
