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Portilla-Fernandez, E.* ; Hwang, S.J.* ; Wilson, R. ; Maddock, J.* ; Hill, W.D.* ; Teumer, A.* ; Mishra, P.P.* ; Brody, J.A.* ; Joehanes, R.* ; Ligthart, S.* ; Ghanbari, M.* ; Kavousi, M.* ; Roks, A.J.M.* ; Danser, A.H.J.* ; Levy, D.* ; Peters, A. ; Ghasemi, S.* ; Schminke, U.* ; Dörr, M.* ; Grabe, H.J.* ; Lehtimäki, T.* ; Kähönen, M.* ; Hurme, M.A.* ; Bartz, T.M.* ; Sotoodehnia, N.* ; Bis, J.C.* ; Thiery, J.* ; Koenig, W.* ; Ong, K.K.* ; Bell, J.T.* ; Meisinger, C. ; Wardlaw, J.M.* ; Starr, J.M.* ; Seissler, J. ; Then, C. ; Rathmann, W.* ; Ikram, M.A.* ; Psaty, B.M.* ; Raitakari, O.T.* ; Völzke, H.* ; Deary, I.J.* ; Wong, A.* ; Waldenberger, M. ; O'Donnell, C.J.* ; Dehghan, A.*

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness.

Eur. J. Epidemiol. 36, 1143-1155 (2021)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cardiovascular Risk Factors ; Common Carotid Intima-media Thickness ; Dna Methylation ; Differentially Methylated Regions ; Epigenome-wide Association Studies ; Mendelian Randomization ; Vascular Outcomes; Hydrocarbon Receptor Repressor; Dna Methylation; Epigenetic Modifications; Mendelian Randomization; Cigarette-smoking; Coronary Events; Blood-pressure; Atherosclerosis; Inflammation; Gene
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 0393-2990
e-ISSN 1573-7284
Journal European Journal of Epidemiology
Quellenangaben Volume: 36, Issue: 11, Pages: 1143-1155 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Independent Research Group Clinical Epidemiology (KEPI)
Institute of Experimental Genetics (IEG)
POF-Topic(s) 30202 - Environmental Health
30201 - Metabolic Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504091-001
G-504000-010
G-502900-001
G-521500-002
DOI 10.1007/s10654-021-00759-z
WOS ID WOS:000658252300003
Scopus ID 85107473695
PubMed ID 34091768
Erfassungsdatum 2021-07-06
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