Mendelian randomization and pleiotropy analysis.

Background: Mendelian randomization (MR) analysis has become popular in inferring and estimating the causality of an exposure on an outcome due to the success of genome wide association studies. Many statistical approaches have been developed and each of these methods require specific assumptions.

Results: In this article, we review the pros and cons of these methods. We use an example of high-density lipoprotein cholesterol on coronary artery disease to illuminate the challenges in Mendelian randomization investigation.

Conclusion: The current available MR approaches allow us to study causality among risk factors and outcomes. However, novel approaches are desirable for overcoming multiple source confounding of risk factors and an outcome in MR analysis.