TY - JOUR
T1 - Targeted next-generation sequencing for genetic variants of left ventricular mass status among community-based adults in Taiwan
AU - Fan, Hsien Yu
AU - Lin, Wan Yu
AU - Lu, Tzu Pin
AU - Chen, Yun Yu
AU - Hsu, Justin Bo Kai
AU - Yu, Sung Liang
AU - Su, Ta Chen
AU - Lin, Hung Ju
AU - Chen, Yang Ching
AU - Chien, Kuo Liong
N1 - Funding Information:
The authors thank the Ministry of Science and Technology of Taiwan for supporting the funding of our work.
Funding Information:
The study was supported by the National Science and Technology Council, Taiwan: MOST 109-2314-B-002-203; MOST 106-2314-B-002-158-MY3.
Publisher Copyright:
Copyright © 2023 Fan, Lin, Lu, Chen, Hsu, Yu, Su, Lin, Chen and Chien.
PY - 2023/1/12
Y1 - 2023/1/12
N2 - 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.
AB - 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.
KW - gene expression
KW - gene network
KW - genetic variants
KW - left ventricular mass
KW - next-generation sequencing
UR - https://www.scopus.com/pages/publications/85147127103
UR - https://www.scopus.com/pages/publications/85147127103#tab=citedBy
U2 - 10.3389/fgene.2022.1064980
DO - 10.3389/fgene.2022.1064980
M3 - Article
AN - SCOPUS:85147127103
SN - 1664-8021
VL - 13
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 1064980
ER -