Targeted next-generation sequencing for genetic variants of left ventricular mass status among community-based adults in Taiwan

Hsien Yu Fan, Wan Yu Lin, Tzu Pin Lu, Yun Yu Chen, Justin Bo Kai Hsu, Sung Liang Yu, Ta Chen Su, Hung Ju Lin, Yang Ching Chen, Kuo Liong Chien

Research output: Contribution to journalArticlepeer-review


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 <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 <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.

Original languageEnglish
Article number1064980
JournalFrontiers in Genetics
Publication statusPublished - Jan 12 2023


  • gene expression
  • gene network
  • genetic variants
  • left ventricular mass
  • next-generation sequencing

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)


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