Wang Congrong, Alfano Rossella, Reimann Brigitte, Hogervorst Janneke, Bustamante Mariona, De Vivo Immaculata, Plusquin Michelle, Nawrot Tim S, Martens Dries S
Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.
ISGlobal, Barcelona, Spain.
Front Genet. 2022 Oct 4;13:934277. doi: 10.3389/fgene.2022.934277. eCollection 2022.
Telomere length at birth determines later life telomere length and potentially predicts ageing-related diseases. However, the genetic and epigenetic settings of telomere length in newborns have not been analyzed. In addition, no study yet has reported how the interplay between genetic variants and genome-wide cytosine methylation explains the variation in early-life telomere length. In this study based on 281 mother-newborn pairs from the ENVIRAGE birth cohort, telomere length and whole-genome DNA methylation were assessed in cord blood and 26 candidate single nucleotide polymorphism related to ageing or telomere length were genotyped. We identified three genetic variants associated with cord blood telomere length and 57 methylation quantitative trait loci (-mQTLs) of which 22 mQTLs confirmed previous findings and 35 were newly identified. Five SNPs were found to have significant indirect effects on cord blood telomere length the mediating CpGs. The association between rs911874 () and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in might have a mediation or modification effect on the genetic difference in newborn telomere length. This novel approach warrants future follow-up studies that are needed to further confirm and extend these findings.
出生时的端粒长度决定了晚年的端粒长度，并可能预测与衰老相关的疾病。然而，新生儿端粒长度的遗传和表观遗传背景尚未得到分析。此外，尚无研究报道基因变异与全基因组胞嘧啶甲基化之间的相互作用如何解释早期端粒长度的差异。在这项基于ENVIRAGE出生队列中281对母婴的研究中，对脐带血中的端粒长度和全基因组DNA甲基化进行了评估，并对26个与衰老或端粒长度相关的候选单核苷酸多态性进行了基因分型。我们鉴定出三个与脐带血端粒长度相关的基因变异和57个甲基化定量性状位点（-mQTLs），其中22个mQTLs证实了先前的发现，35个是新发现的。发现五个单核苷酸多态性对脐带血端粒长度有显著的间接影响——通过介导的CpG。rs911874（）与新生儿端粒长度之间的关联受到附近DNA甲基化的修饰，这通过显著的统计相互作用表明。我们的结果表明，中的DNA甲基化可能对新生儿端粒长度的遗传差异有介导或修饰作用。这种新方法值得未来进行后续研究，以进一步证实和扩展这些发现。
