In:
Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2023-1-12)
Abstract:
Background: Left ventricular mass is a highly heritable disease. Previous studies have suggested common genetic variants to be associated with left ventricular mass; however, the roles of rare variants are still unknown. We performed targeted next-generation sequencing using the TruSight Cardio panel, which provides comprehensive coverage of 175 genes with known associations to 17 inherited cardiac conditions. Methods: We conducted next-generation sequencing using the Illumina TruSight Cardiomyopathy Target Genes platform using the 5% and 95% extreme values of left ventricular mass from community-based participants. After removing poor-quality next-generation sequencing subjects, including call rate & lt;98% and Mendelian errors, 144 participants were used for the analysis. We performed downstream analysis, including quality control, alignment, coverage length, and annotation; after setting filtering criteria for depths more than 60, we found a total of 144 samples and 165 target genes for further analysis. Results: Of the 12,287 autosomal variants, most had minor allele frequencies of & lt;1% (rare frequency), and variants had minor allele frequencies ranging from 1% to 5%. In the multi-allele variant analyses, 16 loci in 15 genes were significant using the false discovery rate of less than .1. In addition, gene-based analyses using continuous and binary outcomes showed that three genes ( CASQ2 , COL5A1 , and FXN ) remained to be associated with left ventricular mass status. One single-nucleotide polymorphism (rs7538337) was enriched for the CASQ2 gene expressed in aorta artery ( p = 4.6 × 10–18), as was another single-nucleotide polymorphism (rs11103536) for the COL5A1 gene expressed in aorta artery ( p = 2.0 × 10–9). Among the novel genes discovered, CASQ2 , COL5A1 , and FXN are within a protein–protein interaction network with known cardiovascular genes. Conclusion: We clearly demonstrated candidate genes to be associated with left ventricular mass. Further studies to characterize the target genes and variants for their functional mechanisms are warranted.
Type of Medium:
Online Resource
ISSN:
1664-8021
DOI:
10.3389/fgene.2022.1064980
DOI:
10.3389/fgene.2022.1064980.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2606823-0
Permalink
