The second analysis conducted was a variant heterogeneity test for global horizontal pleiotropy. Variant heterogeneity is an important metric, but high heterogeneity doesn’t necessarily mean bias or unreliable results; for example, every instrumental variable could have horizontal pleiotropic effects but if they have a mean effect of 0 then there will be no bias, just larger standard errors due to more noise. For analyses that had evidence of high variant heterogeneity (P < 0.05), additional sensitivity MR tests were conducted. The sensitivity tests that were used were the MR Egger test and the weighted median test to examine whether the effect estimate was consistent.
