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
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
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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