RVLV End-diastolic Shape GWAS (UK Biobank)

Heart shape captures variation in cardiac structure beyond traditional phenotypes of mass and volume. Although observational studies have demonstrated associations with cardiometabolic risk factors and diseases, its genetic basis has not been investigated. We utilised cardiovascular magnetic resonance images from 45,683 UK Biobank participants to construct a heart shape atlas from bi-ventricular end-diastolic surface mesh models through principal component (PC) analysis.

Genome-wide association studies were performed on the first 11 PCs that captured 83.6% of shape variance. We identified 45 significant signals, 14 were previously unreported for cardiac traits. Genetically-predicted PCs were associated with cardiometabolic diseases, including heart failure and myocardial infarction. In particular, those representing more spherical hearts were associated with higher atrial fibrillation risk. Our study explores the genetic basis of heart shape for the first time, reporting new loci and biology, as well as polygenic risk scores for exploring genetic relationships of heart shape with cardiometabolic diseases.