α′ increased from 0.01 to 0.1. In scenario 3 (InSIDE satisfied), estimates from the univariable and multivariable MR‐Egger methods were unbiased, whereas in scenario 4 (InSIDE violated), they were biased. Although the causal estimates for both multivariable IVW and multivariable MR‐Egger were biased under scenario 4, the magnitude of bias was less for multivariable MR‐Egger, with the exception of when αj′ was generated from N(0.01,0.004). Precision and power to detect a causal effect were always better for the multivariable MR‐Egger method than univariable MR‐Egger, although the univariable MR‐Egger method detected directional pleiotropy more often. The average value of α′ had no impact on the degree of bias for univariable or multivariable MR‐Egger. βXkcorrelated: Bias for the multivariable IVW method was present in scenarios 3 and 4 only, as in the independently generated setting. In this setting, the InSIDE assumption for univariable MR‐Egger was violated for all 4 scenarios, resulting in biased point estimates of θ 1. However, the multivariable InSIDE assumption was satisfied for scenarios 1, 2, and 3, and so causal estimates from multivariable MR‐Egger were unbiased. When the multivariable InSIDE assumption was violated (scenario 4) the estimates from multivariable MR‐Egger were biased, yet the magnitude of bias was
