Meta-analysis of epigenome-wide association studies of carotid intima-media thickness
Bartz Traci M.; Bell Jordana T.; Bis Joshua C.; Brody Jennifer A.; Danser A. H. Jan; Deary Ian J.; Dehghan Abbas; Dörr Marcus; Ghanbari Mohsen; Ghasemi Sahar; Grabe Hans J.; Hill W. David; Hurme Mikko A.; Hwang Shih-Jen; Ikram M. Arfan; Joehanes Roby; Kavousi Maryam; Koenig Wolfgang; Kähönen Mika; Lehtimäki Terho; Levy Daniel; Ligthart Symen; Maddock Jane; Meisinger Christine; Mishra Pashupati P.; Ong Ken K.; O’Donnell Christopher J.; Peters Annette; Portilla-Fernández Eliana; Psaty Bruce M.; Raitakari Olli T.; Rathmann Wolfgang; Roks Anton J. M.; Schminke Ulf; Seissler Jochen; Sotoodehnia Nona; Starr John M.; Teumer Alexander; Then Cornelia; Thiery Joachim; Völzke Henry; Waldenberger Melanie; Wardlaw Joanna M.; Wilson Rory; Wong Andrew
https://urn.fi/URN:NBN:fi-fe2021093049078
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]