Guidelines for performing Mendelian randomization investigations: update for summer 2023.

Area of Science:

• Epidemiology
• Genetics
• Biostatistics

Background:

• Mendelian randomization (MR) is a powerful method for inferring causal relationships.
• Standardized guidelines are needed for conducting and evaluating MR studies.
• Existing methodologies require clear, accessible documentation for practitioners.

Purpose of the Study:

• To provide comprehensive guidelines for performing Mendelian randomization investigations.
• To assist researchers in analyzing and reporting MR findings.
• To aid journal editors and reviewers in assessing MR manuscripts.

Main Methods:

• The guidelines are structured into ten distinct sections.
• Key areas covered include data sources, genetic variant selection, and harmonization.
• Emphasis is placed on primary, supplementary, and sensitivity analyses, alongside extensions and interpretation.

Main Results:

• The paper presents a structured framework for Mendelian randomization studies.
• It details best practices for statistical analysis and data presentation.
• The guidelines address potential biases and offer methods for robust inference.

Conclusions:

• Adherence to these guidelines will enhance the rigor and reproducibility of Mendelian randomization research.
• The proposed framework promotes transparent reporting and critical appraisal of MR studies.
• These guidelines will be periodically updated to reflect advancements in the field.