Sinkala Musalula, Retshabile Gaone, Mpangase Phelelani T, Bamba Salia, Goita Modibo K, Nembaware Vicky, Elsheikh Samar S M, Heckmann Jeannine, Esoh Kevin, Matshaba Mogomotsi, Adebamowo Clement A, Adebamowo Sally N, Amih Ofon Elvis, Wonkam Ambroise, Ramsay Michele, Mulder Nicola
Division of Computational Biology, Department of Integrative Biomedical Sciences and Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
medRxiv. 2024 Aug 12:2024.08.11.24311816. doi: 10.1101/2024.08.11.24311816.
Epigenetic modifications influence gene expression levels, impact organismal traits, and play a role in the development of diseases. Therefore, variants in genes involved in epigenetic processes are likely to be important in disease susceptibility, and the frequency of variants may vary between populations with African and European ancestries. Here, we analyse an integrated dataset to define the frequencies, associated traits, and functional impact of epigenetic gene variants among individuals of African and European ancestry represented in the UK Biobank. We find that the frequencies of 88.4% of epigenetic gene variants significantly differ between these groups. Furthermore, we find that the variants are associated with many traits and diseases, and some of these associations may be population-specific owing to allele frequency differences. Additionally, we observe that variants associated with traits are significantly enriched for quantitative trait loci that affect DNA methylation, chromatin accessibility, and gene expression. We find that methylation quantitative trait loci account for 71.2% of the variants influencing gene expression. Moreover, variants linked to biomarker traits exhibit high correlation. We therefore conclude that epigenetic gene variants associated with traits tend to differ in their allele frequencies among African and European populations and are enriched for QTLs.
表观遗传修饰影响基因表达水平，影响生物体性状，并在疾病发展中发挥作用。因此，参与表观遗传过程的基因变异可能在疾病易感性中起重要作用，并且变异频率在非洲和欧洲血统的人群之间可能有所不同。在这里，我们分析了一个综合数据集，以确定英国生物银行中非洲和欧洲血统个体中表观遗传基因变异的频率、相关性状和功能影响。我们发现，这些群体之间88.4%的表观遗传基因变异频率存在显著差异。此外，我们发现这些变异与许多性状和疾病相关，并且由于等位基因频率差异，其中一些关联可能具有人群特异性。此外，我们观察到与性状相关的变异在影响DNA甲基化、染色质可及性和基因表达的数量性状位点中显著富集。我们发现甲基化数量性状位点占影响基因表达的变异的71.2%。此外，与生物标志物性状相关的变异表现出高度相关性。因此，我们得出结论，与性状相关的表观遗传基因变异在非洲和欧洲人群中的等位基因频率往往不同，并且在数量性状位点中富集。
