Despite these limitations, for most pairs of complex traits we recommend using LCV instead of MR, as MR methods (including MR Egger) are easily confounded by genetic correlations. MR is more reliable when it is possible to identify variants that are likely to represent valid instruments. For example, an MR analysis identified a causal effect of vitamin D on multiple sclerosis, utilizing genetic variants near genes with well-characterized effects on vitamin D synthesis, metabolism and transport [66]. As another example, cis-eQTLs can be used as genetic instruments, as they are unlikely to be confounded by processes mediated in trans [62-64]; however, this approach has other limitations [63,65].
