Multivariable MR (MVMR) and extensions

Multivariable MR extension of the IVW approach applied to the summary data context. Used to learn about the causal effect of two or more exposures on an outcome. 

All genetic IVs must be associated with at least one exposure. All genetic IVs can be invalid instruments due to pleiotropy as long as the pleiotropy is balanced. Method can be combined with MR-Egger regression to allow for directional pleiotropy. 

References

• Rees JMB, Wood AM, Burgess S. Extending the MR-Egger method for multivariable Mendelian randomization to correct for both measured and unmeasured pleiotropy. Statistics in Medicine 2017;36:4705-4718.
• Burgess S, Thompson SG. Multivariable Mendelian Randomization: The Use of Pleiotropic Genetic Variants to Estimate Causal Effects. American Journal of Epidemiology 2015;181:251-260.

Other terms in 'Pleiotropy-robust two-sample MR methods':

• Generalized summary MR (GSMR)
• IVW (random effects)
• Median-based estimate
• Mode-based estimate
• MR-Egger regression and extensions
• MR-RAPS