Table 1.
Detailed parameters of each GWAS data in the structural equation modeling.
Fig 1.
Flowchart detailing the study design and analytical pipeline.
The workflow encompasses the data preprocessing of single-input GWAS for four age-related eye diseases, multivariable Genomic Structural Equation Modeling (Genomic-SEM) to extract the latent ARED factor, and comprehensive post-processing analyses. SC: Senile cataract, Gla: Glaucoma; AMD: Age-related macular degeneration; DR: Diabetic retinopathy; GWAS: Genome-Wide Association Study; MAGMA: Multi-marker Analysis of GenoMic Annotation; TWAS: Transcriptome-Wide Association Study. (By Figdraw.).
Fig 2.
Genomic risk loci identification and annotation for the latent ARED factor using FUMA.
A Manhattan plot of GWAS summary statistics (only SNPs with P-value ≤ 1 × 10−5 are kept) B Functional consequences of SNPs on genes.C Summary per genomic risk locus. D-F Risky genetic seat locations detected through FUMA. (rs1502593, rs2183836, rs3763764) GWAS: Genome-Wide Association Study; SNPs: single nucleotide polymorphisms.
Fig 3.
The results of fine mapping and transcriptome prediction.
A,B Fine localization analysis identified strong associations at multiple genomic locations (mean.PP > 0.95). (SOX2-OT, SLC24A3) C Manhattan plot of 2 genes that exceeded the criteria for correction for multiple comparisons from the TWAS. D,E FOCUS fine positioning analysis results. (MMAB, SLC24A3) TWAS: Transcriptome-Wide Association Study.
Fig 4.
Transcriptomic and gene-based association analyses.
A Miami plot of Z-scores from the TWAS. B Manhattan plot of the gene-based test as computed by MAGMA based on GWAS summary statistics. Genome wide significance (red dashed line in the plot) was defined at P = 0.05/17766 = 2.814 × 10−6; TWAS: Transcriptome-Wide Association Study; MAGMA: Multi-marker Analysis of GenoMic Annotation; GWAS: Genome-Wide Association Study.
Fig 5.
Disease ontology enrichment analysis using MendelVar.
The bubble plot illustrates the significant enrichment of mapped genes in specific Mendelian disease categories. The x-axis represents the number of genes overlapping with the specific disease ontology, and the y-axis lists the enriched disease terms. The color gradient of the bubbles reflects the empirical P-value, while the size of the bubbles corresponds to the ratio of gene overlap.