Challenges and future directions for Mendelian randomization

Area of Science:

• Genetics
• Epidemiology
• Biostatistics

Background:

• Mendelian randomization (MR) has transitioned from a specialized technique to a mainstream research methodology.
• Existing MR studies often underutilize the full potential of available data and advanced techniques for assumption validation.

Purpose of the Study:

• To provide a bibliometric overview of the MR literature.
• To discuss current practices in conducting MR studies.
• To identify limitations in empirically assessing MR assumptions and causal claims.

Main Methods:

• Bibliometric analysis of Mendelian randomization literature.
• Discussion of empirical validation strategies for MR assumptions.
• Exploration of challenges and opportunities presented by evolving genetic and genomic data.

Main Results:

• The MR field has grown significantly, indicating widespread adoption.
• There is a gap between the potential of available data/techniques and their application in validating MR assumptions.
• Integrating evidence from molecular, cellular, animal, and quasi-experimental studies is crucial for robust causal inference.

Conclusions:

• Future advancements in Mendelian randomization depend on integrating diverse empirical evidence to rigorously assess assumptions and causal claims.
• The evolving landscape of genetic and genomic data presents both challenges and opportunities for the MR framework.
• Enhanced validation strategies are needed to fully realize the potential of MR for understanding causal mechanisms.