Table 1.

Major assumptions of the main methods discussed in this article

Method	Assumptions
IVW fixed effects	All SNPs estimate the same causal effect	Balanced pleiotropy	InSIDE	NOME
IVW random effects		Balanced pleiotropy	InSIDE	NOME
MR-RAPS		Balanced pleiotropy	InSIDE
CAUSE		Balanced pleiotropy	Parametric model + priors
MR-Egger fixed effects	All SNPs estimate the same causal effect		InSIDE	NOME
MR-Egger fixed effects + SIMEX	All SNPs estimate the same causal effect		InSIDE
MR-Egger random effects			InSIDE	NOME
MR-Egger random effects + SIMEX			InSIDE
Bayesian model averaging			InSIDE	NOME
Median			At least 50% of SNPs are valid instruments	NOME
Mode			ZEMPA	NOME
MRMix			ZEMPA	NOME
Heterogeneity penalized			ZEMPA	NOME

(IVW) Inverse variance weighted, (SNPs) single-nucleotide polymorphisms, (InSIDE) instrument strength independent of direct pleiotropic effect, (NOME) no measurement error in the SNP-exposure effect, (MR-RAPS) Mendelian randomization-robust adjusted profile score, (ZEMPA) zero modal pleiotropy assumption, meaning that the mode of the direct pleiotropic effects is zero.