Synonyms: IV1 assumption, first MR assumption

This is the first of the core IV assumptions which states that the IV must be associated with the risk factor of interest.

In MR the aim is to select genetic variants that have been shown to be robustly associated with the risk factor of interest. In most MR studies, this means genetic variants that are associated with an exposure at genome-wide significance and replicated in several independent study samples from the population of interest. The statistical strength of the genetic instrument-risk factor association if ‘weak’ can result in weak instrument bias.

## References

- 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.

## Other terms in 'Sources of bias and limitations in MR':

- Assortative mating
- Canalization
- Collider
- Collider bias
- Confounding
- Dynastic effects
- Exclusion restriction assumption
- 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)
- Reverse causality
- Same underlying population (in two-sample MR)
- Statistical power/efficiency
- Vertical Pleiotropy
- Weak instrument bias
- Winner's curse