MRAD

MRAD provides Mendelian randomization analysis results for Alzheimer's disease by integrating data from MRC IEU OpenGWAS to identify potential therapeutic targets and causal risk or protective factors.

Key Features:

• Hypothesis-free Mendelian randomization analysis: Performs MR analysis on 18,097 exposure traits and 16 AD outcome traits from MRC IEU OpenGWAS, generating 400,274 total data entries.
• Inverse-variance weighted model: Uses IVW as the major analysis method, comprising 73,129 records with 4,840 exposure traits across 10 categories: Disease, Medical laboratory science, Imaging, Anthropometric, Treatment, Molecular trait, Gut microbiota, Past history, Family history, and Lifestyle trait.
• Sensitivity analysis: Conducts robustness assessment of IVW results using six additional models.
• Outcome stratification: Analyzes associations with Alzheimer's disease, early-onset AD, and late-onset AD separately.
• Therapeutic target identification: Identifies novel potential AD therapeutic targets including CD33, TBCA, VPS29, GNAI3, and PSME1 with directional causal associations.

Scientific Applications:

• AD risk factor discovery: Identifies various classes of risk or protective factors for Alzheimer's disease, early-onset AD, and late-onset AD through systematic causal inference.
• Therapeutic target prioritization: Facilitates identification of potential drug targets for Alzheimer's disease, such as CD33 (positively associated) and TBCA, VPS29, GNAI3, PSME1 (negatively associated) with AD outcomes.
• Etiology research: Advances understanding of Alzheimer's disease pathogenesis by evaluating multifactorial causal associations across diverse exposure categories.

Methodology:

The inverse-variance weighted model serves as the major analysis method for Mendelian randomization, with sensitivity analysis conducted using six additional models to assess robustness of results.