Analysis code for: Integrative proteo-genomic analysis identifies VSIG4 and NFKB1 as causal therapeutic targets for sarcoidosis

This repository contains the complete analysis code for a multi-layered proteome-wide cis-pQTL Mendelian randomization (MR) study of sarcoidosis. The pipeline integrates ten analytical modules: (1) forward MR using Wald ratio with FDR correction and Steiger directionality testing; (2) Bayesian colocalization (coloc.abf); (3) eQTL-based summary data-based MR (SMR) and HEIDI testing using eQTLGen whole-blood data; (4) reverse MR with IVW, MR-Egger, weighted median sensitivity analyses and leave-one-out diagnostics; (5) regional association (LocusZoom-style) plots with real LD from 1000 Genomes Phase 3 EUR; (6) single-cell RNA sequencing validation using bronchoalveolar lavage data (GSE184735); (7) druggability assessment (DGIdb 5.0, Open Targets), protein–protein interaction network (STRING), and pathway enrichment (GO and KEGG); (8) independent MR replication using Million Veteran Program (MVP) sarcoidosis GWAS; (9) phenome-wide association (PheWAS) lookup via the NHGRI-EBI GWAS Catalog; and (10) evidence tier classification and heatmap visualization. All scripts are written in R (≥ 4.4.0) and use publicly available summary statistics from the UK Biobank Pharma Proteomics Project (UKB-PPP), FinnGen R12, MVP, and eQTLGen Consortium. External tools include PLINK v1.9 and SMR v1.3.1. All genomic coordinates are on the GRCh38/hg38 assembly.