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

ABSTRACT: 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.

SUBMITTER: Wang C

PROVIDER: S-EPMC9576874 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Wang Congrong C Alfano Rossella R Reimann Brigitte B Hogervorst Janneke J Bustamante Mariona M De Vivo Immaculata I Plusquin Michelle M Nawrot Tim S TS Martens Dries S DS

Frontiers in genetics 20221004

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<i>ON</i>AGE birth cohort, telomere length and whole ...[more]

PMID: 36267401

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Project description:ImportanceLow socioeconomic status is associated with higher all-cause mortality and risks for aging-related diseases. Biological aging is a potential process underlying health conditions related to social disadvantages, which may be present from birth onward.ObjectiveTo evaluate the association of parental socioeconomic status with telomere length (TL) at birth, a marker of biological aging.Design, setting, and participantsThis prospective birth cohort study was conducted among 1504 mother-newborn pairs in Belgium recruited between February 1, 2010, and July 1, 2017.ExposuresParental socioeconomic measures, including maternal educational level, occupation, paternal educational level, and neighborhood income based on median annual household income.Main outcomes and measuresMean relative TL was measured in cord blood and placental tissue. By constructing a principal component, an integrative socioeconomic measure was derived that integrates parental socioeconomic status and neighborhood income. Multivariable adjusted regression analyses were performed to associate the integrative socioeconomic measure and TL at birth.ResultsIn 1026 newborns (517 boys; mean [SD] gestational age, 39.2 [1.4] weeks), a higher socioeconomic status was associated with longer cord blood TL and placental TL. Each unit increment in the integrative socioeconomic status measure was associated with 2.1% (95% CI, 0.9%-3.4%; P < .001) longer cord blood TL in boys, while no association was observed for girls (0.5% longer cord blood TL; 95% CI, -0.9% to 1.8%; P = .50). The sex-specific socioeconomic status interaction revealed a stronger association in boys compared with newborn girls (1.6%; 95% CI, 0.02%-3.3%; P = .047 for interaction). In placental tissue, higher socioeconomic status was associated with 1.8% (95% CI, 0.3%-3.3%; P = .02) longer TL in newborn boys but not in girls (0.4% longer TL; 95% CI, -1.2% to 2.0%; P = .63). For placental tissue, no sex and socioeconomic status interaction on TL was observed (1.4%; 95% CI, -0.5% to 3.4%; P = .16 for interaction).Conclusions and relevanceThis study suggests that parental socioeconomic status is associated with newborn TL, especially in boys. The results indicate that familial social economic factors are associated with the potential cellular longevity of the next generation, with a potential higher transgenerational vulnerability for newborn boys.

Dataset Information

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

Publications

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

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