TY - JOUR T1 - Meta-analysis of epigenome-wide association studies of carotid intima-media thickness. JF - Eur J Epidemiol Y1 - 2021 A1 - Portilla-Fernández, Eliana A1 - Hwang, Shih-Jen A1 - Wilson, Rory A1 - Maddock, Jane A1 - Hill, W David A1 - Teumer, Alexander A1 - Mishra, Pashupati P A1 - Brody, Jennifer A A1 - Joehanes, Roby A1 - Ligthart, Symen A1 - Ghanbari, Mohsen A1 - Kavousi, Maryam A1 - Roks, Anton J M A1 - Danser, A H Jan A1 - Levy, Daniel A1 - Peters, Annette A1 - Ghasemi, Sahar A1 - Schminke, Ulf A1 - Dörr, Marcus A1 - Grabe, Hans J A1 - Lehtimäki, Terho A1 - Kähönen, Mika A1 - Hurme, Mikko A A1 - Bartz, Traci M A1 - Sotoodehnia, Nona A1 - Bis, Joshua C A1 - Thiery, Joachim A1 - Koenig, Wolfgang A1 - Ong, Ken K A1 - Bell, Jordana T A1 - Meisinger, Christine A1 - Wardlaw, Joanna M A1 - Starr, John M A1 - Seissler, Jochen A1 - Then, Cornelia A1 - Rathmann, Wolfgang A1 - Ikram, M Arfan A1 - Psaty, Bruce M A1 - Raitakari, Olli T A1 - Völzke, Henry A1 - Deary, Ian J A1 - Wong, Andrew A1 - Waldenberger, Melanie A1 - O'Donnell, Christopher J A1 - Dehghan, Abbas AB -

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) 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). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

ER -