Synonyms: Exclusion restriction criterion, IV3 assumption, third MR assumption
Known as the third IV assumption, this states that the IV is not related to the outcome other than via the risk factor of interest.
In general, MR this may be violated by horizontal pleiotropy. In MR exploring effects of maternal (or paternal) exposure on offspring, this may be violated by fetal (offspring genotype) (see MR for testing developmental origins).
References
- Evans DM, Moen G-H, Hwang L-D, Lawlor DA, Warrington NM. Elucidating the role of maternal environmental exposures on offspring health and disease using two-sample Mendelian randomization. International Journal of Epidemiology 2019.
- Lawlor DA, Harbord RM, Sterne JAC, Timpson NJ, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Statistic in Medicine 2008;27:1133-1163.
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ (Clinical research ed) 2018;362:k601.
- Lawlor DA, Richmond R, Warrington N et al. Using Mendelian randomization to determine causal effects of pregnancy (intrauterine) exposures on offspring outcomes: Sources of bias and methods for assessing them. . Wellcome Open Research 2017;2:11.
Other terms in 'Sources of bias and limitations in MR':
- Assortative mating
- Canalization
- Collider
- Collider bias
- Confounding
- Dynastic effects
- Harmonization failure (in two-sample MR)
- Homogeneity Assumption
- Horizontal Pleiotropy
- Independence assumption
- InSIDE assumption (in two-sample MR using aggregate data)
- Monotonicity assumption
- MR for testing critical or sensitive periods
- MR for testing developmental origins
- No effect modification assumption (Additional IV assumption)
- Non-linear effects
- Non-overlapping samples (in two-sample MR)
- Overfitting
- Pleiotropy
- Population stratification
- Regression dilution bias (attenuation by errors)
- Relevance assumption
- Reverse causality
- Same underlying population (in two-sample MR)
- Statistical power/efficiency
- Vertical Pleiotropy
- Weak instrument bias
- Winner's curse