New Genetic Loci Implicated in Cardiac Morphology and Function Using Three-Dimensional Population Phenotyping

作者：Chang Lu, Kathryn A. McGurk, Sean L. Zheng, Antonio de Marvao, Paolo Inglese, Wenjia Bai, James S. Ware, Declan P. O’Regan · 发表于：Circulation Genomic and Precision Medicine · 年份：2025 · DOI：10.1161/circgen.124.005116 · 被引用次数：2 · 研究领域：Congenital heart defects research、Cardiomyopathy and Myosin Studies、Cardiac Fibrosis and Remodeling

BACKGROUND: Cardiac remodeling occurs in the mature heart and is a cascade of adaptations in response to stress, which are primed in early life. A key question remains as to the processes that regulate the geometry and motion of the heart and how it adapts to stress. METHODS: We performed spatially resolved phenotyping using machine learning-based analysis of cardiac magnetic resonance imaging in 47 549 UK Biobank participants. We analyzed 16 left ventricular spatial phenotypes, including regional myocardial wall thickness and systolic strain in both circumferential and radial directions. In up to 40 058 participants, genetic associations across the allele frequency spectrum were assessed using genome-wide association studies with imputed genotype participants, and exome-wide association studies and gene-based burden tests using whole-exome sequencing data. We integrated transcriptomic data from the GTEx project and used pathway enrichment analyses to further interpret the biological relevance of identified loci. To investigate causal relationships, we conducted Mendelian randomization analyses to evaluate the effects of blood pressure on regional cardiac traits and the effects of these traits on cardiomyopathy risk. RESULTS: (minor allele frequency 0.5%). The majority of newly discovered loci are found in cardiomyopathy-associated genes, suggesting that they regulate spatially distinct patterns of remodeling in the left ventricle in an adult population. Our causal analysis a...