Fig. 1. Study overview of European ancestry DCM GWAS performed in 14,256 cases and 1,199,156 controls from 16 studies.

Cases were defined as having a clinical diagnosis or unequivocal disease label for DCM (DCM_Narrow) or a more inclusive definition of LV systolic dysfunction, with or without LV dilatation (DCM_Broad), in the absence of CAD, severe valvular heart disease or congenital heart disease. Genetic correlation was performed to identify traits suitable for inclusion in meta-analysis and multitrait analysis of GWAS (MTAG). The MTAG analysis combined DCM GWAS with GWAS of genetically correlated quantitative cardiac magnetic resonance (CMR) imaging-derived traits (DCM MTAG). Downstream analyses included elucidating the genetic architecture of DCM, genomic risk loci annotation and prioritization of candidate genes, integration with single-cell transcriptomics to identify perturbations of candidate gene expression, and generation and evaluation of polygenic risk scores (PGS) for DCM. LVESV, LV end systolic volume; LVEF, LV ejection fraction; strain_circ, global LV circumferential strain. Figure created with BioRender.com.