In this final chapter, we consider the future of Mendelian randomization within the wider context of genetic epidemiology. We divide the chapter into two sections. First, we discuss methodological developments in instrumental variable techniques which enable more sophisticated Mendelian randomization analyses. Secondly, we discuss applied developments, such as advances in genotyping and other high-throughput cell biology techniques, which widen the scope for future Mendelian randomization analyses.


In conclusion, there are still areas of ongoing methodological research in Mendelian randomization, and work is needed to translate existing and future methodological developments into the context of Mendelian randomization for applied researchers. This is fueled to a large extent by increasing data availability: new exposure variables, increasing detail of genetic measurements, and publicly-available data resources. These are likely to provide further insights into causal mechanisms, and further scope for methodological and applied developments in the future.

Relevant papers to chapter:

Section 11.1.2 (Non-linear exposure–outcome relationships). S. Burgess, N.M. Davies, S.G. Thompson. Instrumental variable analysis with a nonlinear exposure–outcome relationship. Epidemiology 2014; 25(6):877-885.

Section 11.1.3 (Untangling the causal effects of related exposures). S. Burgess, S.G. Thompson. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am. J. Epidemiol. 2014.

Section 11.1.3 (Untangling the causal effects of related exposures). S. Burgess, D.F. Freitag, H. Khan, D.N. Gorman, S.G. Thompson. Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. PLoS One 2014; 9(10):e108891.

Sections 11.1.4 (Elucidating the direction of causation) and 11.1.5 (Investigating indirect and direct effects). S. Burgess, R.M. Daniel, A.S. Butterworth, S.G. Thompson, EPIC-InterAct. Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways. Int. J. Epidemiol. 2014.

Section 11.2.4 (Published data and two-sample Mendelian randomization). S. Burgess, R.A. Scott, N.J. Timpson, G. Davey Smith, S.G. Thompson. Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors. Submitted manuscript.