Synonyms: Exclusion restriction criterion, IV3 assumption, third MR assumption
Known as the third MR assumption or the "no horizontal pleiotropy assumption", this states that the instrumental variable (IV) is not related to the outcome other than via the exposure of interest.
In MR, this assumption may be violated by horizontal pleiotropy of the genetic variants being used as an IV. For example, in MR studies exploring the effects of maternal (or paternal) exposures on offspring outcomes, this assumption may be violated by fetal (offspring genotype). As, in practice, this is the most common MR assumption likely to be violated, there are an increasing number of methods that aim to identify and account for bias due to horizontal pleiotropy. 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; 48: 861-875.
- 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
- Conditional F-statistic for multiple exposures
- Confounding
- F-statistic
- Harmonization (in two-sample MR)
- Homogeneity Assumption
- Horizontal Pleiotropy
- Independence assumption
- INstrument Strength Independent of Direct Effect (InSIDE) assumption
- Intergenerational (or dynastic) effects
- Monotonicity assumption
- MR for testing critical or sensitive periods
- MR for testing developmental origins
- No effect modification assumption
- NO Measurement Error (NOME) assumption
- Non-linear MR
- Non-overlapping samples (in two-sample MR)
- Overfitting
- Pleiotropy
- Population stratification
- R-squared
- Regression dilution bias (attenuation by errors)
- Relevance assumption
- Reverse causality
- Same underlying population (in two-sample MR)
- Statistical power and efficiency
- Vertical pleiotropy
- Weak instrument bias
- Winner's curse