A systematic review of GWAS on CMR imaging traits: genetic insights into cardiovascular structure, function, and diseases.

Abstract

Cardiac magnetic resonance (CMR) imaging enables precise quantification of cardiac structure/function in biobanks, facilitating genetic investigation of cardiovascular traits. Genome-wide association studies (GWAS) have emerged as a useful tool to identify common and rare genetic variants associated with cardiovascular diseases (CVDs). We conducted a systematic review of CMR-based cardiac trait GWAS to generate an overview of phenotypes evaluated, loci identified and relationships with CVD outcomes. We identified 149 risk loci associated with chamber-specific cardiac traits, revealing fundamental insights into cardiac genetic architecture. Our findings demonstrate that ventricular structure and function are predominantly governed by genes such as TTN (identified in 47.1% of studies) and BAG3 (29.4%) showing consistent associations across both left and right ventricular traits. In contrast, aortic measures were strongly associated with ELN variants (23.5%), highlighting specialised genetic control of vascular properties. Notably, several genes influence multiple cardiac chambers, with TTN variants associated with both left and right ventricular volumes and function, while BAG3 and PTPN11 regulate biventricular contractility, and TBX5 impacts ventricular and atrial development. By identifying key genetic variants linked with CMR-derived cardiac traits, this review enhances our understanding of the genetics of CVDs and other medical conditions. British Heart Foundation Accelerator Award (AA/18/6/34223) and NIHR University College London Hospitals Biomedical Research Centre.