The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a vestige
of embryonic development.1,2 The function of these trabeculae in adults and their genetic architecture are unknown. To
investigate this we performed a genome-wide association study using fractal analysis of trabecular morphology as an
image-derived phenotype in 18,096 UK Biobank participants. We identified 16 significant loci containing genes associated
with haemodynamic phenotypes and regulation of cytoskeletal arborisation.3,4 Using biomechanical simulations and human
observational data, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Through
genetic association studies with cardiac disease phenotypes and Mendelian randomisation, we find a causal relationship
between trabecular morphology and cardiovascular disease risk. These findings suggest an unexpected role for myocardial
trabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity, and reveal their
influence on susceptibility to disease