Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases

Abstract Molecular mechanisms at the intersection of inflammation and cardiovascular diseases (CVD) among Africans are still unknown. We performed an epigenome-wide association study to identify loci associated with serum C-reactive protein (marker of inflammation) among Ghanaians and further assess...

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Autores principales:	Felix P. Chilunga, Peter Henneman, Andrea Venema, Karlijn A. C. Meeks, Ana Requena-Méndez, Erik Beune, Frank P. Mockenhaupt, Liam Smeeth, Silver Bahendeka, Ina Danquah, Kerstin Klipstein-Grobusch, Adebowale Adeyemo, Marcel M.A.M Mannens, Charles Agyemang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/e27c8165c7f54426b80c72d01efa9ab4
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spelling	oai:doaj.org-article:e27c8165c7f54426b80c72d01efa9ab42021-12-02T17:48:01ZGenome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases10.1038/s41525-021-00213-92056-7944https://doaj.org/article/e27c8165c7f54426b80c72d01efa9ab42021-06-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00213-9https://doaj.org/toc/2056-7944Abstract Molecular mechanisms at the intersection of inflammation and cardiovascular diseases (CVD) among Africans are still unknown. We performed an epigenome-wide association study to identify loci associated with serum C-reactive protein (marker of inflammation) among Ghanaians and further assessed whether differentially methylated positions (DMPs) were linked to CVD in previous reports, or to estimated CVD risk in the same population. We used the Illumina Infinium® HumanMethylation450 BeadChip to obtain DNAm profiles of blood samples in 589 Ghanaians from the RODAM study (without acute infections, not taking anti-inflammatory medications, CRP levels < 40 mg/L). We then used linear models to identify DMPs associated with CRP concentrations. Post-hoc, we evaluated associations of identified DMPs with elevated CVD risk estimated via ASCVD risk score. We also performed subset analyses at CRP levels ≤10 mg/L and replication analyses on candidate probes. Finally, we assessed for biological relevance of our findings in public databases. We subsequently identified 14 novel DMPs associated with CRP. In post-hoc evaluations, we found that DMPs in PC, BTG4 and PADI1 showed trends of associations with estimated CVD risk, we identified a separate DMP in MORC2 that was associated with CRP levels ≤10 mg/L, and we successfully replicated 65 (24%) of previously reported DMPs. All DMPs with gene annotations (13) were biologically linked to inflammation or CVD traits. We have identified epigenetic loci that may play a role in the intersection between inflammation and CVD among Ghanaians. Further studies among other Africans are needed to confirm our findings.Felix P. ChilungaPeter HennemanAndrea VenemaKarlijn A. C. MeeksAna Requena-MéndezErik BeuneFrank P. MockenhauptLiam SmeethSilver BahendekaIna DanquahKerstin Klipstein-GrobuschAdebowale AdeyemoMarcel M.A.M MannensCharles AgyemangNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Felix P. Chilunga Peter Henneman Andrea Venema Karlijn A. C. Meeks Ana Requena-Méndez Erik Beune Frank P. Mockenhaupt Liam Smeeth Silver Bahendeka Ina Danquah Kerstin Klipstein-Grobusch Adebowale Adeyemo Marcel M.A.M Mannens Charles Agyemang Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases
description	Abstract Molecular mechanisms at the intersection of inflammation and cardiovascular diseases (CVD) among Africans are still unknown. We performed an epigenome-wide association study to identify loci associated with serum C-reactive protein (marker of inflammation) among Ghanaians and further assessed whether differentially methylated positions (DMPs) were linked to CVD in previous reports, or to estimated CVD risk in the same population. We used the Illumina Infinium® HumanMethylation450 BeadChip to obtain DNAm profiles of blood samples in 589 Ghanaians from the RODAM study (without acute infections, not taking anti-inflammatory medications, CRP levels < 40 mg/L). We then used linear models to identify DMPs associated with CRP concentrations. Post-hoc, we evaluated associations of identified DMPs with elevated CVD risk estimated via ASCVD risk score. We also performed subset analyses at CRP levels ≤10 mg/L and replication analyses on candidate probes. Finally, we assessed for biological relevance of our findings in public databases. We subsequently identified 14 novel DMPs associated with CRP. In post-hoc evaluations, we found that DMPs in PC, BTG4 and PADI1 showed trends of associations with estimated CVD risk, we identified a separate DMP in MORC2 that was associated with CRP levels ≤10 mg/L, and we successfully replicated 65 (24%) of previously reported DMPs. All DMPs with gene annotations (13) were biologically linked to inflammation or CVD traits. We have identified epigenetic loci that may play a role in the intersection between inflammation and CVD among Ghanaians. Further studies among other Africans are needed to confirm our findings.
format	article
author	Felix P. Chilunga Peter Henneman Andrea Venema Karlijn A. C. Meeks Ana Requena-Méndez Erik Beune Frank P. Mockenhaupt Liam Smeeth Silver Bahendeka Ina Danquah Kerstin Klipstein-Grobusch Adebowale Adeyemo Marcel M.A.M Mannens Charles Agyemang
author_facet	Felix P. Chilunga Peter Henneman Andrea Venema Karlijn A. C. Meeks Ana Requena-Méndez Erik Beune Frank P. Mockenhaupt Liam Smeeth Silver Bahendeka Ina Danquah Kerstin Klipstein-Grobusch Adebowale Adeyemo Marcel M.A.M Mannens Charles Agyemang
author_sort	Felix P. Chilunga
title	Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases
title_short	Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases
title_full	Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases
title_fullStr	Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases
title_full_unstemmed	Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases
title_sort	genome-wide dna methylation analysis on c-reactive protein among ghanaians suggests molecular links to the emerging risk of cardiovascular diseases
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e27c8165c7f54426b80c72d01efa9ab4
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Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases

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