Figure 1
The design concept of this study. The accuracy of estimating causality using MR analyses is based on the following three assumptions: the instrumental variable (IV) associate with the exposure (IV assumption 1). This assumption can be satisfied by ensuring F statistic > 10 and that SNPs are selected using genome-wide significance levels (P < 5 × 10–8), (2) The IV is independent of combined influence of all confounders (IV assumption 2). For the same population and reference, we assess correlation of linkage disequilibrium between SNPs associated robustly with exposure and SNPs linked to possible known confounders. If the correlation coefficient is higer (i.e. r2 ≥ 0.5), the corresponding selected SNPs will be discarded. (3) The IV is independent of the outcome given the exposure and confounders (IV assumption 3), Horzontal pleiotroy, that IVs influence the outcome through alternative pathways other than the exposure could violate this assumption. It can be checked by using MR-Egger regression and MR-PRESSO method.
