Whole-Genome Differentially Hydroxymethylated DNA Regions among Twins Discordant for Cardiovascular Death
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Study Samples
2.3. DNA Sample Collection
2.4. Genome-Wide Methylation (5mC) Measures
2.5. Measurement of Whole-Genome Hydroxymethylation (5hmC)
2.5.1. Genomic DNA Preparation
2.5.2. 5hmC Capture and Sequencing
2.6. Assessment of Covariates
2.7. Follow-up and Assessment of Endpoints
2.8. Statistical Analysis
2.8.1. Estimation of Peripheral Blood Leukocyte Composition
2.8.2. Identification of Signature Differentially Hydroxymethylated Regions
2.9. Bioinformatic Analysis
2.9.1. Bioinformatic Visualization
2.9.2. Functional Enrichment Analysis
2.9.3. DNA Motif Enrichment Analysis
3. Results
3.1. Characteristics of the Study Twin Pairs Discordant for Cardiovascular Death
3.2. Differentially Hydroxymethylated Regions (DhMRs) from Monozygotic (MZ) Twin Pairs Discordant for Cardiovascular Death (CVD-dMZ)
3.2.1. Genetic Characteristics of the 102 DhMRs
3.2.2. Generalizability Validation in Dizygotic (DZ) Twin Pairs Discordant for Cardiovascular Death (CVD-dDZ)
3.3. Functional Enrichment Analysis of DhMRs
3.4. Enriched DNA Motifs
4. Discussion
4.1. Consistency with Prior Studies
4.2. Mechanisms
4.3. Limitations and Advantages
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Annotation 1 | Total DhMRs | Hyper-DhMRs | Hypo-DhMRs |
---|---|---|---|
n | 102 | 84 | 18 |
Exons1 | 2 (2.0 3) | 2 (2.3 3) | 0 |
ncRNA2 | 1 (50 4) | 1 (50 4) | 0 |
protein-coding2 | 1 (50 4) | 1 (50 4) | 0 |
Pseudo2 | 0 | 0 | 0 |
snoRNA2 | 0 | 0 | 0 |
Intergenic regions1 | 47 (46 3) | 42 (50 3) | 5 (28 3) |
ncRNA | 14 (30 4) | 13 (31 4) | 1 (20 4) |
protein-coding | 30 (64 4) | 26 (62 4) | 4 (80 4) |
pseudo | 3 (6 4) | 3 (7 4) | 0 |
snoRNA | 0 | 0 | 0 |
Introns1 | 49 (48 3) | 37 (44 3) | 12 (67 3) |
ncRNA | 11 (22 4) | 10 (27 4) | 1 (8 4) |
protein-coding | 35 (71 4) | 25 (68 4) | 10 (83 4) |
pseudo | 3 (6 4) | 1 (3 4) | 1 (8 4) |
snoRNA | 1 (2 4) | 1 (3 4) | 0 |
TSS1 | 2 (2.0 3) | 1 (1.2 3) | 1 (5.6 3) |
ncRNA | 0 | 0 | 0 |
protein-coding | 1 (50 4) | 0 | 1 (100 4) |
pseudo | 1 (50 4) | 1 (100 4) | 0 |
snoRNA | 0 | 0 | 0 |
TTS 1 | 2 (2.0 3) | 2 (2.3 3) | 0 |
ncRNA | 0 | 0 | 0 |
protein-coding | 2 (100 4) | 2 (100 4) | 0 |
pseudo | 0 | 0 | 0 |
snoRNA | 0 | 0 | 0 |
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Dai, J.; Leung, M.; Guan, W.; Guo, H.-T.; Krasnow, R.E.; Wang, T.J.; El-Rifai, W.; Zhao, Z.; Reed, T. Whole-Genome Differentially Hydroxymethylated DNA Regions among Twins Discordant for Cardiovascular Death. Genes 2021, 12, 1183. https://doi.org/10.3390/genes12081183
Dai J, Leung M, Guan W, Guo H-T, Krasnow RE, Wang TJ, El-Rifai W, Zhao Z, Reed T. Whole-Genome Differentially Hydroxymethylated DNA Regions among Twins Discordant for Cardiovascular Death. Genes. 2021; 12(8):1183. https://doi.org/10.3390/genes12081183
Chicago/Turabian StyleDai, Jun, Ming Leung, Weihua Guan, Han-Tian Guo, Ruth E. Krasnow, Thomas J. Wang, Wael El-Rifai, Zhongming Zhao, and Terry Reed. 2021. "Whole-Genome Differentially Hydroxymethylated DNA Regions among Twins Discordant for Cardiovascular Death" Genes 12, no. 8: 1183. https://doi.org/10.3390/genes12081183
APA StyleDai, J., Leung, M., Guan, W., Guo, H.-T., Krasnow, R. E., Wang, T. J., El-Rifai, W., Zhao, Z., & Reed, T. (2021). Whole-Genome Differentially Hydroxymethylated DNA Regions among Twins Discordant for Cardiovascular Death. Genes, 12(8), 1183. https://doi.org/10.3390/genes12081183