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DNA methylation modules associate with incident cardiovascular disease and cumulative risk factor exposure
- Source :
- Repisalud, Instituto de Salud Carlos III (ISCIII), Clinical Epigenetics
- Publication Year :
- 2019
- Publisher :
- BioMed Central, 2019.
-
Abstract
- Background Epigenome-wide association studies using DNA methylation have the potential to uncover novel biomarkers and mechanisms of cardiovascular disease (CVD) risk. However, the direction of causation for these associations is not always clear, and investigations to-date have often failed to replicate at the level of individual loci. Methods Here, we undertook module- and region-based DNA methylation analyses of incident CVD in the Women’s Health Initiative (WHI) and Framingham Heart Study Offspring Cohort (FHS) in order to find more robust epigenetic biomarkers for cardiovascular risk. We applied weighted gene correlation network analysis (WGCNA) and the Comb-p algorithm to find methylation modules and regions associated with incident CVD in the WHI dataset. Results We discovered two modules whose activation correlated with CVD risk and replicated across cohorts. One of these modules was enriched for development-related processes and overlaps strongly with epigenetic aging sites. For the other, we showed preliminary evidence for monocyte-specific effects and statistical links to cumulative exposure to traditional cardiovascular risk factors. Additionally, we found three regions (associated with the genes SLC9A1, SLC1A5, and TNRC6C) whose methylation associates with CVD risk. Conclusions In sum, we present several epigenetic associations with incident CVD which reveal disease mechanisms related to development and monocyte biology. Furthermore, we show that epigenetic modules may act as a molecular readout of cumulative cardiovascular risk factor exposure, with implications for the improvement of clinical risk prediction.
- Subjects :
- 0301 basic medicine
Epigenomics
Male
Oncology
medicine.medical_specialty
Cumulative Exposure
Disease
030204 cardiovascular system & hematology
Bioinformatics
Epigenesis, Genetic
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Framingham Heart Study
Internal medicine
Genetics
medicine
Humans
Gene Regulatory Networks
Genetic Predisposition to Disease
Epigenetics
Risk factor
Molecular Biology
Genetics (clinical)
Aged
030304 developmental biology
Genetic association
0303 health sciences
business.industry
Research
Methylation
DNA Methylation
Middle Aged
Human genetics
3. Good health
030104 developmental biology
Cardiovascular Diseases
DNA methylation
CpG Islands
Female
business
Software
Developmental Biology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Repisalud, Instituto de Salud Carlos III (ISCIII), Clinical Epigenetics
- Accession number :
- edsair.doi.dedup.....e0228272ec008e55020ad7faabf4aad3