ArticleCirculation. Genomic and precision medicine2025
New Genetic Loci Implicated in Cardiac Morphology and Function Using Three-Dimensional Population Phenotyping.
Article in Circulation. Genomic and precision medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Effects of Schizophrenia, Bipolar Disorder, and Depression on Cardiopulmonary and Abdominal Organ Structure.Biological psychiatry global open science · 2026Article
- Translating genome-wide association studies at multiple scales: Drug target prioritization, cellular architectures, and organ imaging.Cell genomics · 2026Review
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8 authors.
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Abstract
backgroundCardiac 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.
methodsWe 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.
resultsWe found 42 loci associated with cardiac structure and contractility, many of which reveal patterns of spatial organization in the heart. Whole-exome sequencing revealed 3 additional variants not captured by the genome-wide association study, including a missense variant in
conclusionsThese findings provide a comprehensive description of the pathways that orchestrate heart development and cardiac remodeling. These data highlight the role that cardiomyopathy-associated genes have on the regulation of spatial adaptations in those without known disease.
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