Gillian L Meeks, Brooke Scelza, Hana M Asnake, Sean Prall, Etienne Patin, Alain Froment, Maud Fagny, Lluis Quintana-Murci, Brenna M Henn, Shyamalika Gopalan
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引用次数: 0
摘要
衰老与人类 DNA 甲基化的全基因组变化有关,这促进了表观遗传年龄预测模型的开发。然而,这些模型大多主要是针对欧洲血统的个体进行训练的,而且都没有考虑甲基化定量性状位点(meQTL)的影响。为了填补这些空白,我们分析了 3 个未被充分研究的人群中年龄、基因型和 CpG 甲基化之间的关系:非洲中部的巴卡人(n = 35)、非洲南部的≠Khomani San 人(n = 52)和非洲南部的 Himba 人(n = 51)。我们发现,与欧洲血统的个体相比,已发表的预测方法在这些群体中产生的平均误差更大,并发现未计算在内的 DNA 序列变异可能是导致准确性下降的重要因素。我们利用 DNA 基因型与 CpG 甲基化之间的关联信息,开发出了一种受 meQTL 影响最小的年龄预测方法,并证明该模型在广泛的遗传背景下仍然准确。有趣的是,我们还发现,在我们的队列中,年龄较大的个体和表观遗传年龄加速度相对较低的个体往往携带更多的表观遗传年龄降低基因变异,这表明遗传因素可以通过一种新的机制影响寿命。
Common DNA sequence variation influences epigenetic aging in African populations
Aging is associated with genome-wide changes in DNA methylation in humans, facilitating the development of epigenetic age prediction models. However, most of these models have been trained primarily on European-ancestry individuals, and none account for the impact of methylation quantitative trait loci (meQTL). To address these gaps, we analyzed the relationships between age, genotype, and CpG methylation in 3 understudied populations: central African Baka (n = 35), southern African ≠Khomani San (n = 52), and southern African Himba (n = 51). We find that published prediction methods yield higher mean errors in these cohorts compared to European-ancestry individuals, and find that unaccounted-for DNA sequence variation may be a significant factor underlying this loss of accuracy. We leverage information about the associations between DNA genotype and CpG methylation to develop an age predictor that is minimally influenced by meQTL, and show that this model remains accurate across a broad range of genetic backgrounds. Intriguingly, we also find that the older individuals and those exhibiting relatively lower epigenetic age acceleration in our cohorts tend to carry more epigenetic age-reducing genetic variants, suggesting a novel mechanism by which heritable factors can influence longevity.