R Scripts for Four-Layer Mendelian Randomization and Druggable Target Prioritization between OSAHS and its cardiometabolic diseases

Description

This repository contains the R scripts used for the four-layer Mendelian randomization (MR) analysis presented in the manuscript entitled "Integrated genetic-proteomic analysis of OSAHS and cardiometabolic comorbidities: dissecting causality and prioritizing drug targets." The workflow is structured as follows: Genetic Correlation and Causal Direction:​ Estimation of genetic correlations between Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) and ten cardiometabolic traits using Linkage Disequilibrium Score Regression (LDSC) and Latent Causal Variable (LCV) models to select phenotypes for downstream analysis. Independent Causal Effects:​ Implementation of bidirectional MR, multivariable MR (MVMR), and mediation MR to elucidate independent effects and shared mechanisms among seven selected diseases. Candidate Gene Mapping:​ Integration of Bayesian colocalization analysis and summary-data-based MR (SMR) to identify candidate genes associated with disease risk. Proteome-wide MR and Druggability:​ Prioritization of druggable protein targets using cis-protein quantitative trait loci (cis-pQTLs) and proteome-wide MR analysis. Software Requirements: R (version >= 4.0.0) Key R packages: TwoSampleMR, MendelianRandomization, Coloc, ieugwasr, LDlinkR, and ggplot2. Usage: The main script (main_analysis.R) sequentially executes the four steps described above. Users should ensure access to the required GWAS summary statistics (e.g., from IEU OpenGWAS, GWAS Catalog, or FinnGen) prior to running the scripts.

Institutions

• China Medical University

  Liaoning, Shenyang

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