Dataset Information

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

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 <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.

SUBMITTER: Fan HY

PROVIDER: S-EPMC9879005 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Fan Hsien-Yu HY Lin Wan-Yu WY Lu Tzu-Pin TP Chen Yun-Yu YY Hsu Justin BoKai JB Yu Sung-Liang SL Su Ta-Chen TC Lin Hung-Ju HJ Chen Yang-Ching YC Chien Kuo-Liong KL

Frontiers in genetics 20230112

<b>Background:</b> 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. <b>Methods:</b> We conducted next-generation sequencing using the Illumina TruS ...[more]

PMID: 36712865

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Project description:Background: Elevated blood pressure (BP) is associated with target organ damage, such as left ventricular hypertrophy (LVH), in childhood. However, it is unclear if children who resolve elevated BP have reduced levels of left ventricular mass index (LVMI). This study aimed to examine the association between change in BP status over 2 years and LVMI among Chinese children. Methods: Data were from 1,183 children aged 6-11 years at baseline in 2017 who were followed up in 2019 in the Huantai Childhood Cardiovascular Health Cohort Study. Change in BP status over 2 years from baseline to follow-up was categorized as: persistent normal BP, resolved elevated BP (elevated BP at baseline, normal BP at follow-up), incident elevated BP (normal BP at baseline, elevated BP at follow-up), and persistent elevated BP. Elevated BP status was defined according to national reference standards as systolic or diastolic BP levels ≥ sex-, age-, and height-specific 95th percentiles. Results: LVMI levels were lowest in children with persistent normal BP (30.13 g/m2.7), higher in those with incident elevated BP (31.27 g/m2.7), and highest in those with persistent elevated BP (33.26 g/m2.7). However, LVMI levels in those who had resolved elevated BP (30.67 g/m2.7) were similar to those with persistent normal BP. In the fully adjusted model, compared with children with persistent normal BP, those with persistent elevated BP and incident elevated BP had higher LVMI at follow-up (ß = 3.131, p < 0.001; ß = 1.143, p = 0.041, respectively). In contrast, those who had resolved elevated BP did not have a significantly higher LVMI (ß = 0.545, p = 0.194) than those with persistent normal BP. Conclusion: Developing or maintaining elevated BP over a 2-year period in childhood associated with higher levels of LVMI, but those able to resolve their elevated BP status over the same period had LVMI levels that were similar with those who had normal BP at both time points. Thus, it is important to identify children with elevated BP at early time and to take effective measures to lower their BP levels, thereby reducing high LVMI levels and related cardiovascular diseases in the future.

Dataset Information

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

Publications

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

Similar Datasets

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