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

Autor: Shih-Jen Hwang, Jordana T. Bell, Olli T. Raitakari, Mikko Hurme, Joanna M. Wardlaw, W. David Hill, Joshua C. Bis, Traci M. Bartz, Anton J.M. Roks, John M. Starr, Wolfgang Koenig, M. Arfan Ikram, Eliana Portilla-Fernandez, Alexander Teumer, Annette Peters, Mika Kähönen, Ian J. Deary, Maryam Kavousi, Nona Sotoodehnia, Joachim Thiery, Jennifer A. Brody, Melanie Waldenberger, Ulf Schminke, Abbas Dehghan, Hans J. Grabe, Roby Joehanes, Symen Ligthart, Daniel Levy, Bruce M. Psaty, A.H. Jan Danser, Wolfgang Rathmann, Henry Völzke, Andrew Wong, Mohsen Ghanbari, Jochen Seissler, Terho Lehtimäki, Ken K. Ong, Jane Maddock, Rory P. Wilson, Christopher J. O'Donnell, Cornelia Then, Christine Meisinger, Pashupati P. Mishra, Sahar Ghasemi, Marcus Dörr
Přispěvatelé: Portilla-Fernández, Eliana [0000-0003-4105-8586], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, BioMediTech, Epidemiology, Internal Medicine
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Oncology
medicine.medical_specialty
Epidemiology
Differentially methylated regions
Aryl hydrocarbon receptor repressor
Coronary Artery Disease
030204 cardiovascular system & hematology
Carotid Intima-Media Thickness
Coronary artery disease
03 medical and health sciences
Epigenome
0302 clinical medicine
SDG 3 - Good Health and Well-being
Risk Factors
Internal medicine
Mendelian randomization
Medicine
Vascular outcomes
Humans
ddc:610
cardiovascular diseases
Stroke
Cardiovascular risk factors
Epigenome-wide association studies
DNA methylation
business.industry
medicine.disease
humanities
3142 Public health care science
environmental and occupational health
ddc
030104 developmental biology
Cross-Sectional Studies
CpG site
Intima-media thickness
cardiovascular system
Common carotid intima-media thickness
business
Meta-Analysis
Zdroj: European Journal of Epidemiology
Portilla-fernández, E, Hwang, S, 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 2021, ' Meta-analysis of epigenome-wide association studies of carotid intima-media thickness ', European Journal of Epidemiology . https://doi.org/10.1007/s10654-021-00759-z
European Journal of Epidemiology, 36(11), 1143-1155. Springer Netherlands
ISSN: 1573-7284
0393-2990
DOI: 10.1007/s10654-021-00759-z
Popis: Funder: Nederlandse Organisatie voor Wetenschappelijk Onderzoek; doi: http://dx.doi.org/10.13039/501100003246
Funder: ZonMw; doi: http://dx.doi.org/10.13039/501100001826
Funder: Research Institute for Diseases in the Elderly
Funder: Ministerie van Onderwijs, Cultuur en Wetenschap; doi: http://dx.doi.org/10.13039/501100003245
Funder: Health Promotion Administration, Ministry of Health and Welfare; doi: http://dx.doi.org/10.13039/100013227
Funder: Municipality of Rotterdam
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.
Databáze: OpenAIRE
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