Table 3. Selected issues to inference from Mendelian randomization.

Specific research field	Issues	Comments
Biological mechanisms	Pleiotropy	It occurs when genetic variants are associated with many kinds of risk factors.
	Canalization	A biological compensatory mechanism that adapts to changes caused by genetic variation and does not reflect the effects of the actual expected genetic variants.
Non-Mendelian inheritance	Linkage disequilibrium	Other variables that are associated with the genetic variants used as an IV affect the outcome.
	Effect modification	When confounding occurs due to some specific third-party variable for the relationship between an IV and a potential exposure.
Population effects	Population stratification	The population included in the study is divided into distinct subpopulations.
	Ascertainment effects	The fraction of a genetic variants of the population included in the study is different from that of the real population, and also if specific results in the study design have a reverse causation.

IV, instrumental variable.