Meta-analysis of epigenome-wide association studies of carotid intima-media thickness.
Eliana Portilla-FernándezShih-Jen HwangRory WilsonJane MaddockW David HillAlexander TeumerPashupati P MishraJennifer A BrodyRoby JoehanesSymen LigthartMohsen GhanbariMaryam KavousiAnton J M RoksA H Jan DanserDaniel LevyAnnette PetersSahar GhasemiUlf SchminkeMarcus DörrHans J GrabeTerho LehtimäkiMika KähönenMikko A HurmeTraci M BartzNona SotoodehniaJoshua C BisJoachim ThieryWolfgang KoenigKen K OngJordana T BellChristine MeisingerJoanna M WardlawJohn M StarrJochen SeisslerCornelia ThenWolfgang RathmannM Arfan IkramBruce M PsatyOlli T RaitakariHenry VölzkeIan J DearyAndrew WongMelanie WaldenbergerChristopher J O'DonnellAbbas DehghanPublished in: European journal of epidemiology (2021)
Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = -0.0264, p value = 3.5 × 10-8) in the discovery panel and was replicated in replication panel (beta = -0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10-13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.
Keyphrases
- dna methylation
- cardiovascular risk factors
- cardiovascular disease
- genome wide
- coronary artery disease
- gene expression
- metabolic syndrome
- systematic review
- copy number
- cardiovascular events
- small molecule
- type diabetes
- atrial fibrillation
- optical coherence tomography
- randomized controlled trial
- percutaneous coronary intervention
- high throughput
- acute coronary syndrome
- risk assessment
- smoking cessation
- heart failure
- case control
- left ventricular
- coronary artery bypass grafting
- climate change
- genome wide identification