Copy Number Variants (CNVs) contribute to 3-10% of isolated Congenital Heart Disease (CHD) cases, but their roles in disease pathogenesis are often unclear. Traditionally, diagnostics have focused on protein-coding genes, overlooking the pathogenic potential of non-coding regions constituting 99% of the genome. Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in development and disease.
In this study, we systematically analyzed candidate lncRNAs overlapping with clinically validated CNVs in 1,363 CHD patients from the Cytogenomics of Cardiovascular Malformations (CCVM) Consortium. We identified heart-expressed lncRNAs, constructed a gene regulatory network using Weighted Gene Co-expression Network Analysis (WGCNA), and identified gene modules significantly associated with heart development. Functional enrichment analyses and network visualizations were conducted to elucidate the roles of these lncRNAs in cardiac development and disease. The code is stably archived at https://doi.org/10.5281/zenodo.13799847.
We identified 18 lncRNA candidate genes within modules significantly correlated with heart tissue, highlighting their potential involvement in CHD pathogenesis. Notably, lncRNAs such as lnc-STK32C-3, lnc-TBX20-1, and CRMA demonstrated strong associations with known CHD genes. Strikingly, while only 7.6% of known CHD genes were impacted by...

Identification of Long Non-coding RNA Candidate Disease Genes Associated with Clinically Reported CNVs in Congenital Heart Disease

10.1101/2024.09.30.615967