Mendelian randomisation in ophthalmology: An overview and practical guide for clinicians

Area of Science:

• Epidemiology
• Genetics
• Ophthalmology

Background:

• Mendelian randomisation (MR) utilizes natural genetic variation for causal inference.
• Rigorous application of MR advances understanding and clinical translation.
• Misuse and misinterpretation of MR are increasingly prevalent, risking spurious scientific findings.

Purpose of the Study:

• To highlight the importance of rigorous application and interpretation of Mendelian randomisation.
• To caution against the misuse and misinterpretation of MR studies.
• To emphasize the need for critical appraisal of MR in ophthalmic research.

Main Methods:

• Leveraging natural genetic variation to strengthen causal inference.
• Applying a rigorous framework for evidence interpretation.
• Triangulating MR results with other lines of evidence.

Main Results:

• MR is a powerful tool when applied correctly.
• Violations of assumptions and lack of gene-environment equivalence can negate clinical translation.
• Overreliance on MR without other evidence can lead to misleading causal claims.

Conclusions:

• Critical appraisal of Mendelian randomisation studies is essential.
• Researchers and clinicians must be equipped to interpret MR studies, especially in ophthalmology.
• Ensuring proper methodology and interpretation is key to avoiding spurious findings and enabling meaningful clinical translation.