Fig. 3: Locus annotation and candidate gene scoring prioritize genes at risk loci and important biological pathways and processes in DCM pathogenesis.

a, Among all genes located within genomic risk loci (1,970 genes), candidate genes were selected based on proximity and being among the top three genes predicted using PoPS or V2G (380 candidate genes). Sixty-two genes were prioritized at 62 loci after scoring highest among the eight predictors. b, Pathway enrichment analysis of prioritized genes, highlighting pathways related to muscle structural constituents. Enrichment of effector genes within Gene Ontology pathways was performed using Fisher’s one-sided test with Bonferroni adjustment of P values for the total number of pathways tested. c, Schematic overview of pathways and processes highlighted in DCM pathogenesis, manually curated from pathway enrichment analysis and published literature. Genes with existing evidence of being Mendelian causes of cardiomyopathy are highlighted in bold. Asterisk indicates moderate or definitive evidence of causing cardiomyopathy³⁰. GO:BP, Gene Ontology: Biological Process; GO:MF, Gene Ontology: Molecular Function; KEGG, Kyoto Encyclopedia of Genes and Genomes; REAC (Reactome Pathway Database); ER, endoplasmic reticulum. a and c were created with BioRender.com.