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

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

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

SPRINGER
doi:10.1007/s10654-021-00759-z
URI
https://link.springer.com/article/10.1007/s10654-021-00759-z
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Julkaisun pysyvä osoite on:
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.

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