Chilunga Felix P, Henneman Peter, Venema Andrea, Meeks Karlijn A C, Requena-Méndez Ana, Beune Erik, Mockenhaupt Frank P, Smeeth Liam, Bahendeka Silver, Danquah Ina, Klipstein-Grobusch Kerstin, Adeyemo Adebowale, Mannens Marcel M A M, Agyemang Charles
Department of Public Health, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Genetics, Amsterdam Reproduction & Development research institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
NPJ Genom Med. 2021 Jun 11;6(1):46. doi: 10.1038/s41525-021-00213-9.
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.
非洲人群中炎症与心血管疾病（CVD）交叉点的分子机制仍不清楚。我们进行了一项全表观基因组关联研究，以确定加纳人群中与血清C反应蛋白（炎症标志物）相关的基因座，并进一步评估之前报告中差异甲基化位点（DMPs）是否与CVD相关，或与同一人群中估计的CVD风险相关。我们使用Illumina Infinium® HumanMethylation450 BeadChip获得了来自RODAM研究的589名加纳人的血液样本的DNA甲基化谱（无急性感染，未服用抗炎药物，CRP水平<40mg/L）。然后，我们使用线性模型来识别与CRP浓度相关的DMPs。事后分析中，我们评估了已识别的DMPs与通过ASCVD风险评分估计的CVD风险升高之间的关联。我们还在CRP水平≤10mg/L时进行了亚组分析，并对候选探针进行了重复分析。最后，我们在公共数据库中评估了我们研究结果的生物学相关性。随后，我们确定了14个与CRP相关的新DMPs。在事后评估中，我们发现PC、BTG4和PADI1中的DMPs显示出与估计的CVD风险相关的趋势，我们在MORC2中确定了一个单独的与CRP水平≤10mg/L相关的DMP，并且我们成功重复了之前报告的65个（24%）DMPs。所有具有基因注释的DMPs（13个）在生物学上都与炎症或CVD特征相关。我们已经确定了可能在加纳人群炎症与CVD交叉点起作用的表观遗传基因座。需要在其他非洲人群中进行进一步研究以证实我们的发现。
