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Longitudinal changes in the genetic and environmental influences on the epigenetic clocks across old age: Evidence from two twin cohorts.

ABSTRACT: BACKGROUND:Measures based on DNA methylation, epigenetic clocks, have recently gained attraction as predictors of mortality and age-related pathologies. However, the origins of variation in these measures are not well understood. METHODS:In a pooled sample of 104 Swedish and Danish twin pairs, we estimated, at the mean age of 70 (baseline) and 79?years (follow-up), the genetic and environmental influences on the Horvath and Levine clocks. FINDINGS:A model incorporating additive genetic (A) and person-specific environmental (E) influences best explained the variation in both clocks. Heritability was estimated at 55% at baseline and at 51% at follow-up for the Horvath clock and 34% at baseline and 41% at follow-up for the Levine clock. For the Horvath clock, new sources of A influences emerged at follow-up, whereas for the Levine clock, the same A influences accounted for the genetic variance at both measurement occasions. The cross-time phenotypic correlations, 0·52 for the Horvath clock and 0·36 for the Levine clock, were mediated primarily by genetic factors, whereas the person-specific environmental factors were completely different at the two measurement occasions. INTERPRETATION:For both clocks, new sources of person-specific environmental influences emerge with age. The epigenetic clocks might thus be responsive to new environmental stimuli even at old age. FUND: NIH (R01;AG04563;AG10175;AG028555) the MacArthur Foundation Research Network on Successful Aging, FAS/FORTE (97:0147:1B;2009-0795), Swedish Research Council (825-2007-7460;825-2009-6141;521-2013-8689;2015-03255;2015-06796;2018-02077), FORTE (2013-2292), the Strategic Research Program in Epidemiology at KI, VELUX FOUNDATION, NIA (P01-AG08761), the EU (FP7/2007-2011;259679) and The Danish National Program for Research Infrastructure 2007 (9-063256).

SUBMITTER: Jylhava J

PROVIDER: S-EPMC6413471 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Longitudinal changes in the genetic and environmental influences on the epigenetic clocks across old age: Evidence from two twin cohorts.

Jylhävä Juulia J Hjelmborg Jacob J Soerensen Mette M Munoz Elizabeth E Tan Qihua Q Kuja-Halkola Ralf R Mengel-From Jonas J Christensen Kaare K Christiansen Lene L Hägg Sara S Pedersen Nancy L NL Reynolds Chandra A CA

EBioMedicine 20190128

<h4>Background</h4>Measures based on DNA methylation, epigenetic clocks, have recently gained attraction as predictors of mortality and age-related pathologies. However, the origins of variation in these measures are not well understood.<h4>Methods</h4>In a pooled sample of 104 Swedish and Danish twin pairs, we estimated, at the mean age of 70 (baseline) and 79 years (follow-up), the genetic and environmental influences on the Horvath and Levine clocks.<h4>Findings</h4>A model incorporating addi ...[more]

PMID: 30704927

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Project description:Eating behaviors during childhood are related both to children's diet quality and to their weight status. A better understanding of the determinants of eating behavior during childhood is essential for carrying out effective dietary interventions.We assessed the contribution of genetic and environmental factors to variations in selected eating behaviors in early and late childhood. Information on eating behaviors came from questionnaires administered to parents of children participating in the Quebec Newborn Twin Study when the twins were 2.5 and 9 years old (n = 692 children). Dichotomous variables were derived and analyzed using structural equation modeling, as part of a classic twin study design. We performed univariate and bivariate longitudinal analyses to quantify sources of variation and covariation across ages, for several eating behavior traits.We found moderate to strong heritability for traits related to appetite such as eating too much, not eating enough and eating too fast. Univariate analysis estimates varied from 0.71 (95% CI: 0.49, 0.87) to 0.89 (0.75, 0.96) in younger children and from 0.44 (0.18, 0.66) to 0.56 (0.28, 0.78) in older children. Bivariate longitudinal analyses indicated modest to moderate genetic correlations across ages (r(A) varying from 0.34 to 0.58). Common genetic influences explained 17% to 43% of the phenotypic correlation between 2.5 and 9 years for these appetite-related behaviors. In 9-year-old children, food acceptance traits, such as refusing to eat and being fussy about food, had high heritability estimates, 0.84 (0.63, 0.94) and 0.85 (0.59, 0.96) respectively, while in younger children, the shared environment (i.e., common to both twins) contributed most to phenotypic variance. Variances in meal-pattern-related behaviors were mostly explained by shared environmental influences.Genetic predispositions explain a large part of the variations in traits related to appetite during childhood, though our results suggest that as children get older, appetite-related behaviors become more sensitive to environmental influences outside the home. Still, for several traits environmental influences shared by twins appear to have the largest relative importance. This finding supports the notion that familial context has considerable potential to influence the development of healthy eating habits throughout childhood.

Dataset Information

Longitudinal changes in the genetic and environmental influences on the epigenetic clocks across old age: Evidence from two twin cohorts.

Publications

Longitudinal changes in the genetic and environmental influences on the epigenetic clocks across old age: Evidence from two twin cohorts.

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