Prevention & lipidsCohort study
DNA Methylation Signatures of Cardiovascular Health Provide Insights Into Diseases
- Epigenome-wide association study with multicohort replication and prospective analyses
- 5 cohorts
- discovery and multicohort replication
- two-sample Mendelian randomization
- multivariable prospective analyses
Authors' conclusion
We identified new DNAm signatures for CVH across diverse cohorts. Our analyses indicate that multiple biological pathways may be relevant to the observed association between CVH and clinical outcomes.
Study context
- Population
- 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, enrolment 1989–2012)5 cohorts
- Outcome
- DNAm loci (CpGs) associated with Life's Essential 8 score (CVH)
Main finding
As reported in the abstract
Cytosine-phosphate-guanines (CpGs) associated with Life's Essential 8 score (FDR<0.05 discovery, Bonferroni-corrected P<0.05 replication)
609
CpGs with heterogeneity <0.2 in replication
414 [68.0%]
Observational data: associations, not effects.
Further findings
Enrichment for phenotypes in the epigenome-wide association studies (EWAS) Catalog
- Stroke enrichment 29-fold
- P = 2.4e-15
- Ischemic heart disease enrichment 21-fold
- P = 7.4e-38
- Pathway enrichment and phenome-wide search linked CpGs to inflammatory or autoimmune phenotypes
Two-sample Mendelian randomization
- CpGs significantly associated with ten phenotypes (261 CpG-phenotype pairs) at FDR<0.05
- 141
- Hypomethylation at cg20544516 (MIR33B and SREBF1) associated with lower stroke risk
- P = 8.1e-6
Cardiovascular health (CVH) DNA methylation (DNAm) score and clinical outcomes (per SD increase)
- Decrease in risk of incident cardiovascular disease (CVD)
- 19% to 32%
- Decrease in risk of CVD mortality
- 28% to 40%
- Decrease in risk of all-cause mortality
- 27% to 45%
- multivariable prospective analyses; ranges across cohorts
Original publication
Summarised from the published abstract; every number is checked against it