MR Dictionary

MR for testing critical or sensitive periods

As genetic variants are fixed at conception, in general, they can be seen to reflect a lifecourse predisposition to a particular trait. This makes MR less prone to regression dilution bias, but such genetic variants might be unsuited to testing the effects of exposures that are believed to act during critical (a time period in which the exposure is hypothesised to solely have its effect) or sensitive (a period during which the exposure is hypothesised to have the greatest effect) periods. 

Some extensions of MR, such as multivariable MR, are available that can help identify critical periods. These methods generally require variation in the association between the genetic variants and the exposure across the lifecourse. As genome-wide association studies (GWASs) of trajectories (e.g., change in weight or height across infancy childhood and into early adulthood) are undertaken, they may also provide genetic instrumental variables (IVs) that could be used in MR to compare change in an exposure between two ages with change in the same exposure between two later ages and compare these to see if there are differences in the effect of that exposure at different ages on an outcome of interest. However, this method is uncommon and likely to need very large sample sizes. 


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