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Genetic regulation of newborn telomere length is mediated and modified by DNA methylation
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 g...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576874/ https://www.ncbi.nlm.nih.gov/pubmed/36267401 http://dx.doi.org/10.3389/fgene.2022.934277 |
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author | Wang, Congrong Alfano, Rossella Reimann, Brigitte Hogervorst, Janneke Bustamante, Mariona De Vivo, Immaculata Plusquin, Michelle Nawrot, Tim S. Martens, Dries S. |
author_facet | Wang, Congrong Alfano, Rossella Reimann, Brigitte Hogervorst, Janneke Bustamante, Mariona De Vivo, Immaculata Plusquin, Michelle Nawrot, Tim S. Martens, Dries S. |
author_sort | Wang, Congrong |
collection | PubMed |
description | 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 ENVIRONAGE 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 cis methylation quantitative trait loci (cis-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 via the mediating CpGs. The association between rs911874 (SOD2) and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in cis 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. |
format | Online Article Text |
id | pubmed-9576874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95768742022-10-19 Genetic regulation of newborn telomere length is mediated and modified by DNA methylation Wang, Congrong Alfano, Rossella Reimann, Brigitte Hogervorst, Janneke Bustamante, Mariona De Vivo, Immaculata Plusquin, Michelle Nawrot, Tim S. Martens, Dries S. Front Genet Genetics 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 ENVIRONAGE 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 cis methylation quantitative trait loci (cis-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 via the mediating CpGs. The association between rs911874 (SOD2) and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in cis 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. Frontiers Media S.A. 2022-10-04 /pmc/articles/PMC9576874/ /pubmed/36267401 http://dx.doi.org/10.3389/fgene.2022.934277 Text en Copyright © 2022 Wang, Alfano, Reimann, Hogervorst, Bustamante, De Vivo, Plusquin, Nawrot and Martens. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Wang, Congrong Alfano, Rossella Reimann, Brigitte Hogervorst, Janneke Bustamante, Mariona De Vivo, Immaculata Plusquin, Michelle Nawrot, Tim S. Martens, Dries S. Genetic regulation of newborn telomere length is mediated and modified by DNA methylation |
title | Genetic regulation of newborn telomere length is mediated and modified by DNA methylation |
title_full | Genetic regulation of newborn telomere length is mediated and modified by DNA methylation |
title_fullStr | Genetic regulation of newborn telomere length is mediated and modified by DNA methylation |
title_full_unstemmed | Genetic regulation of newborn telomere length is mediated and modified by DNA methylation |
title_short | Genetic regulation of newborn telomere length is mediated and modified by DNA methylation |
title_sort | genetic regulation of newborn telomere length is mediated and modified by dna methylation |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576874/ https://www.ncbi.nlm.nih.gov/pubmed/36267401 http://dx.doi.org/10.3389/fgene.2022.934277 |
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