Show Notes
Rios Coronado PE et al., Cell - A multi-ancestry GWAS in >61,000 veterans identifies CXCL12 as a top locus influencing whether the right or left coronary tree supplies the posterior heart; fetal expression, spatial transcriptomics, deep-learning regulatory maps, and mouse heterozygous knockdown link CXCL12 regulation to coronary dominance. Key terms: CXCL12, coronary dominance, GWAS, fetal heart development, mouse model.
Study Highlights:
A GWAS of coronary dominance in 61,043 genotyped participants revealed moderate heritability and ten genome-wide significant loci, with the strongest signal near CXCL12 in both European- and African-ancestry groups. Genetic, eQTL, and deep-learning chromatin analyses indicate dominance-associated variants modulate CXCL12 regulatory elements and expression in vascular cell types. Spatial transcriptomics and fetal heart imaging show CXCL12 expression where dominance is established, and Cxcl12 haploinsufficiency in mice shifts septal artery dominance, supporting a causal role. The CXCL12 locus partially colocalizes with coronary artery disease signals, linking developmental patterning to adult disease risk.
Conclusion:
Common regulatory variation at the CXCL12 locus influences coronary artery patterning established in fetal development; modulating CXCL12 levels alters artery placement in mice and suggests developmental pathways could be targeted for revascularization.
QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-04-16.
Scope: article metadata and core scientific claims from the narration, excluding analogies, intro/outro, and music.
Factual QC score: 10/10.
Metadata QC score: 10/10.
Supported core claims: 8.
Claims flagged for review: 0.
Metadata checks passed: 4.
Metadata issues found: 0.
QC result: Pass.
Music:
Enjoy the music based on this article at the end of the episode.
Article title:
CXCL12 drives natural variation in coronary artery anatomy across diverse populations
First author:
Rios Coronado PE
Journal:
Cell
DOI:
10.1016/j.cell.2025.02.005
Reference:
Rios Coronado PE, Zhou J, Fan X, et al. CXCL12 drives natural variation in coronary artery anatomy across diverse populations. Cell. 2025;188:1784–1806. doi:10.1016/j.cell.2025.02.005
License:
CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/)
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