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. Grabe; Terho 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

doi:10.1007/s10654-021-00759-z

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: Artikkeli › Scientific › vertaisarvioitu

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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.

Alkuperäiskieli	Englanti
Julkaisu	EUROPEAN JOURNAL OF EPIDEMIOLOGY
Vuosikerta	36
Numero	11
DOI - pysyväislinkit	https://doi.org/10.1007/s10654-021-00759-z
Tila	Julkaistu - 2021
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

Jufo-taso 2

!!ASJC Scopus subject areas

Epidemiology

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10.1007/s10654-021-00759-zLisenssi: CC BY

Portilla-Fernández2021_Article_Meta-analysisOfEpigenome-wideAFinal published version, 1,39 MBLisenssi: CC BY

http://urn.fi/URN:NBN:fi:tuni-202106296099Lisenssi: CC BY

Siteeraa tätä

Portilla-Fernández, 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., ... Dehghan, A. (2021). Meta-analysis of epigenome-wide association studies of carotid intima-media thickness. EUROPEAN JOURNAL OF EPIDEMIOLOGY, 36(11). https://doi.org/10.1007/s10654-021-00759-z

@article{26cc35a59ffc4183b68a16c518a54348,

title = "Meta-analysis of epigenome-wide association studies of carotid intima-media thickness",

abstract = "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.",

keywords = "Cardiovascular risk factors, Common carotid intima-media thickness, Differentially methylated regions, DNA methylation, Epigenome-wide association studies, Mendelian randomization, Vascular outcomes",

author = "Eliana Portilla-Fern{\'a}ndez and Hwang, {Shih Jen} and Rory Wilson and Jane Maddock and Hill, {W. David} and Alexander Teumer and Mishra, {Pashupati P.} and Brody, {Jennifer A.} and Roby Joehanes and Symen Ligthart and Mohsen Ghanbari and Maryam Kavousi and Roks, {Anton J.M.} and Danser, {A. H.Jan} and Daniel Levy and Annette Peters and Sahar Ghasemi and Ulf Schminke and Marcus D{\"o}rr and Grabe, {Hans J.} and Terho Lehtim{\"a}ki and Mika K{\"a}h{\"o}nen and Hurme, {Mikko A.} and Bartz, {Traci M.} and Nona Sotoodehnia and Bis, {Joshua C.} and Joachim Thiery and Wolfgang Koenig and Ong, {Ken K.} and Bell, {Jordana T.} and Christine Meisinger and Wardlaw, {Joanna M.} and Starr, {John M.} and Jochen Seissler and Cornelia Then and Wolfgang Rathmann and Ikram, {M. Arfan} and Psaty, {Bruce M.} and Raitakari, {Olli T.} and Henry V{\"o}lzke and Deary, {Ian J.} and Andrew Wong and Melanie Waldenberger and O{\textquoteright}Donnell, {Christopher J.} and Abbas Dehghan",

note = "Funding Information: HJG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm and Janssen Cilag. He has received research funding from the German Research Foundation (DFG), the German Ministry of Education and Research (BMBF), the DAMP Foundation, Fresenius Medical Care, the EU {"}Joint Programme Neurodegenerative Disorders (JPND) and the European Social Fund (ESF){"}. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

doi = "10.1007/s10654-021-00759-z",

language = "English",

volume = "36",

journal = "EUROPEAN JOURNAL OF EPIDEMIOLOGY",

issn = "0393-2990",

publisher = "Springer Verlag",

number = "11",

}

Portilla-Fernández, E, Hwang, SJ, Wilson, R, Maddock, J, Hill, WD, Teumer, A, Mishra, PP, Brody, JA, Joehanes, R, Ligthart, S, Ghanbari, M, Kavousi, M, Roks, AJM, Danser, AHJ, Levy, D, Peters, A, Ghasemi, S, Schminke, U, Dörr, M, Grabe, HJ, Lehtimäki, T , Kähönen, M , Hurme, MA, Bartz, TM, Sotoodehnia, N, Bis, JC, Thiery, J, Koenig, W, Ong, KK, Bell, JT, Meisinger, C, Wardlaw, JM, Starr, JM, Seissler, J, Then, C, Rathmann, W, Ikram, MA, Psaty, BM, Raitakari, OT, Völzke, H, Deary, IJ, Wong, A, Waldenberger, M, O’Donnell, CJ & Dehghan, A 2021, 'Meta-analysis of epigenome-wide association studies of carotid intima-media thickness', EUROPEAN JOURNAL OF EPIDEMIOLOGY, Vuosikerta 36, Nro 11. https://doi.org/10.1007/s10654-021-00759-z

TY - JOUR

T1 - Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

AU - Portilla-Fernández, Eliana

AU - Hwang, Shih Jen

AU - Wilson, Rory

AU - Maddock, Jane

AU - Hill, W. David

AU - Teumer, Alexander

AU - Mishra, Pashupati P.

AU - Brody, Jennifer A.

AU - Joehanes, Roby

AU - Ligthart, Symen

AU - Ghanbari, Mohsen

AU - Kavousi, Maryam

AU - Roks, Anton J.M.

AU - Danser, A. H.Jan

AU - Levy, Daniel

AU - Peters, Annette

AU - Ghasemi, Sahar

AU - Schminke, Ulf

AU - Dörr, Marcus

AU - Grabe, Hans J.

AU - Lehtimäki, Terho

AU - Kähönen, Mika

AU - Hurme, Mikko A.

AU - Bartz, Traci M.

AU - Sotoodehnia, Nona

AU - Bis, Joshua C.

AU - Thiery, Joachim

AU - Koenig, Wolfgang

AU - Ong, Ken K.

AU - Bell, Jordana T.

AU - Meisinger, Christine

AU - Wardlaw, Joanna M.

AU - Starr, John M.

AU - Seissler, Jochen

AU - Then, Cornelia

AU - Rathmann, Wolfgang

AU - Ikram, M. Arfan

AU - Psaty, Bruce M.

AU - Raitakari, Olli T.

AU - Völzke, Henry

AU - Deary, Ian J.

AU - Wong, Andrew

AU - Waldenberger, Melanie

AU - O’Donnell, Christopher J.

AU - Dehghan, Abbas

N1 - Funding Information: HJG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm and Janssen Cilag. He has received research funding from the German Research Foundation (DFG), the German Ministry of Education and Research (BMBF), the DAMP Foundation, Fresenius Medical Care, the EU "Joint Programme Neurodegenerative Disorders (JPND) and the European Social Fund (ESF)". Publisher Copyright: © 2021, The Author(s).

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Cardiovascular risk factors

KW - Common carotid intima-media thickness

KW - Differentially methylated regions

KW - DNA methylation

KW - Epigenome-wide association studies

KW - Mendelian randomization

KW - Vascular outcomes

U2 - 10.1007/s10654-021-00759-z

DO - 10.1007/s10654-021-00759-z

M3 - Article

AN - SCOPUS:85107473695

SN - 0393-2990

VL - 36

JO - EUROPEAN JOURNAL OF EPIDEMIOLOGY

JF - EUROPEAN JOURNAL OF EPIDEMIOLOGY

IS - 11

ER -

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

Abstrakti

Julkaisufoorumi-taso

!!ASJC Scopus subject areas

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