Unraveling the Shared Genetic Architecture and Molecular Mechanisms Linking Cardiovascular Traits and Glaucoma: A Comprehensive Cross‐Trait Analysis
Junfei Huang, Zejun Chen, Mengqing Lin, Bingyu Xu, Qiang Liu, Zhengran Li, Jianping Gao, Guoguo Yi, Min FuABSTRACT
Background
Recent data have indicated a high comorbidity link between cardiovascular characteristics and the risk of glaucoma (Gla), demonstrating a strong comorbidity relationship that warrants investigation into their shared molecular mechanisms and genetic makeup. This study aims to identify shared genetic loci and molecular mechanisms linking cardiovascular traits to glaucoma.
Methods
The genetic overlap between Gla and cardiovascular diseases was examined using genome‐wide association study datasets. Analysis across multiple traits revealed common genomic regions and overlapping gene associations. Pathway analysis via Multi‐marker Analysis of Genomic Annotation and expression quantitative trait loci validation explored functional associations. Single nucleotide polymorphism heritability enrichment was evaluated through linkage disequilibrium.
Results
We detected notable genomic links between eight cardiovascular traits and Gla. The pleiotropic analysis under composite null hypothesis approach revealed 9948 genome‐wide significant loci ( p < 0.001), among which 71 showed strong colocalization evidence. Cross‐validation through functional mapping and annotation, Multi‐marker Analysis of Genomic Annotation, and Summary‐based Mendelian randomization analyses identified 24 pleiotropic genes, including six robust candidates ( BCAS3 , BICC1 , FAM213A , ITGB5 , NUP160 , and TNS1 ).
Conclusions
This study reveals key genetic connections between cardiovascular traits and Gla, identifying pleiotropic loci and six validated genes as potential targets for early detection and treatment. These findings lay the groundwork for further investigation into the systemic‐ocular interplay linking Gla with cardiovascular disease.