AUTHOR=Wang Congrong , Alfano Rossella , Reimann Brigitte , Hogervorst Janneke , Bustamante Mariona , De Vivo Immaculata , Plusquin Michelle , Nawrot Tim S. , Martens Dries S. 

TITLE=Genetic regulation of newborn telomere length is mediated and modified by DNA methylation

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.934277

DOI=10.3389/fgene.2022.934277

ISSN=1664-8021

ABSTRACT=<p>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 ENVIR<italic>ON</italic>AGE 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 <italic>cis</italic> methylation quantitative trait loci (<italic>cis</italic>-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 <italic>via</italic> the mediating CpGs. The association between rs911874 (<italic>SOD2</italic>) and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in <italic>cis</italic> 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.</p>