Directional horizontal pleiotropy, where a genetic instrument has an effect on an outcome independent of its influence on the exposure, can be a problem in MR analysis, particularly when multiple genetic variants of unknown function are used. We therefore firstly tested for directional horizontal pleiotropy using the MR Egger intercept test, as previously described by Hagenaars, Gale, Deary and Harris 70. If the MR Egger intercept test had a significant P-value (P < 0.05) then it was excluded from the analysis. However, no tests were excluded due to directional horizontal pleiotropy.
