Challenges and future directions for Mendelian randomization

Mendelian randomization has evolved from a niche methodology to a widely adopted research approach. In this Perspective, we briefly present a bibliometric analysis of the Mendelian randomization literature to inform a discussion of how Mendelian randomization studies are conducted and how they do not fully realize the potential of the data and techniques available to empirically examine the reliability of assumptions. We propose that future progress will depend on integrating empirical evidence from molecular, cellular, animal and quasi-experimental studies to assess its assumptions and causal claims. We also highlight how the shifting landscape of genetic and genomic data presents new challenges and opportunities for the Mendelian randomization framework, providing a deeper understanding of causal mechanisms.