Code for OPERA and GRS analyses

Decoding Primary Open-Angle Glaucoma: A Multi-Omics Approach to Identify Druggable Effector Genes Data availiable The European, East Asian, African, Latin American, IOP_dependent and IOP_independent POAG GWAS summary statistics Download links are provided in Supplementary Table 1. The GRS analyses were performed using individual-level genotype and phenotype data from UK Biobank under approved access. Researchers can apply for data access through the UK Biobank Access Management System (https://www.ukbiobank.ac.uk/). Retinal eQTL data should be requested from the original study authors. The whole blood eQTLs, sQTLs, mQTLs, caQTLs, pQTLs summary statistics Download links are provided in Supplementary Table 2. OPERA analysis prerequisites To perform the OPERA analysis, the following input files were prepared: GWAS summary statistics for the traits subjected to colocalization analysis. The GWAS datasets downloaded from the links provided in the article contain sufficient information for the analyses; however, format conversion is required prior to analysis. Detailed GWAS format specifications are available at https://yanglab.westlake.edu.cn/software/gcta/#COJO. LD-clumped, genome-wide significant and independent loci derived from the GWAS summary statistics.In this study, LD clumping was performed using PLINK 2, and the corresponding command lines are provided in LD_clump.txt. The reference panel (--bfile 1kgv3EUR ) was based on the 1000 Genomes Project Phase 3 European reference panel. The reference data can be downloaded from https://zenodo.org/records/10515792. A file specifying the locations of the xQTL datasets (xqtllist.txt), together with the corresponding xQTL files in BESD format. Generating BESD format files for retinal eQTL and pQTL data is described in data_preprocessing.txt, whereas BESD format files for the other QTL datasets are directly provided. Individual-level SNP genotype data (in PLINK binary format) from a reference population for LD estimation.In this study, the European ancestry (EUR) reference panel from the 1000 Genomes Project Phase 3 was used. The OPERA analysis code is provided in opera.txt. A detailed description of the OPERA workflow and implementation is available at: https://github.com/wuyangf7/OPERA. Variants frequency, functional, and annotation analyses The code for calculating the IQR of SNPs frequencies is provided in IQR.txt. The code for calculating the Pearson r² of SNPs effect sizes across different populations is provided in pearson_r2.txt. SNPs functional annotation and related trait analyses were performed using the SNP2GENE function of the FUMA platform. The platform default parameters were used for the analysis. A detailed tutorial is available at https://fuma.ctglab.nl/tutorial#snp2gene. Genetic risk score (GRS) analysis GRS analyses were conducted using PLINK 2.The code used for the GRS analysis is provided in GRS.txt. Detailed documentation and implementation guidelines are available at:https://www.cog-genomics.org/plink/2.0/. The code for calculating the AUC and R² of GRS is provided in grs_r2_auc.txt, and the DeLong test code for comparing differences in GRS AUC is provided in compare_auc.txt. NEDREX Drug Target Analysis The NEDREX drug target analysis was performed on Cytoscape using the NEDREX platform. Detailed parameter settings are described in the Methods section of the article. A detailed NEDREX tutorial is available at https://nedrex.net/tutorial/methods.html.