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

Eliana Portilla-Fernández, Shih Jen Hwang, Rory Wilson, Jane Maddock, W. David Hill, Alexander Teumer, Pashupati P. Mishra, Jennifer A. Brody, Roby Joehanes, Symen Ligthart, Mohsen Ghanbari, Maryam Kavousi, Anton J.M. Roks, A. H.Jan Danser, Daniel Levy, Annette Peters, Sahar Ghasemi, Ulf Schminke, Marcus Dörr, Hans J. GrabeTerho Lehtimäki, Mika Kähönen, Mikko A. Hurme, Traci M. Bartz, Nona Sotoodehnia, Joshua C. Bis, Joachim Thiery, Wolfgang Koenig, Ken K. Ong, Jordana T. Bell, Christine Meisinger, Joanna M. Wardlaw, John M. Starr, Jochen Seissler, Cornelia Then, Wolfgang Rathmann, M. Arfan Ikram, Bruce M. Psaty, Olli T. Raitakari, Henry Völzke, Ian J. Deary, Andrew Wong, Melanie Waldenberger, Christopher J. O’Donnell, Abbas Dehghan

Tutkimustuotos: ArticleScientificvertaisarvioitu

Abstrakti

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.

AlkuperäiskieliEnglanti
JulkaisuEUROPEAN JOURNAL OF EPIDEMIOLOGY
DOI - pysyväislinkit
TilaE-pub ahead of print - kesäkuuta 2021
OKM-julkaisutyyppiA1 Alkuperäisartikkeli

Julkaisufoorumi-taso

  • Jufo-taso 2

!!ASJC Scopus subject areas

  • Epidemiology

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