Longitudinal DNA methylation in the Lothian Birth Cohorts of 1921 and 1936
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PROVIDER: EGAC00001000218 | EGA |
REPOSITORIES: EGA
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The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936.
Marioni Riccardo E RE Shah Sonia S McRae Allan F AF Ritchie Stuart J SJ Muniz-Terrera Graciela G Harris Sarah E SE Gibson Jude J Redmond Paul P Cox Simon R SR Pattie Alison A Corley Janie J Taylor Adele A Murphy Lee L Starr John M JM Horvath Steve S Visscher Peter M PM Wray Naomi R NR Deary Ian J IJ
International journal of epidemiology 20150122 4
<h4>Background</h4>The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability.<h4>Methods</h4>DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed o ...[more]
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Project description:Data Access Committee EGAC00001001376
| EGAC00001001376 | EGA
Project description:BackgroundDNA methylation outlier burden has been suggested as a potential marker of biological age. An outlier is typically defined as DNA methylation levels at any one CpG site that are three times beyond the inter-quartile range from the 25th or 75th percentiles compared to the rest of the population. DNA methylation outlier burden (the number of such outlier sites per individual) increases exponentially with age. However, these findings have been observed in small samples.ResultsHere, we showed an association between age and log10-transformed DNA methylation outlier burden in a large cross-sectional cohort, the Generation Scotland Family Health Study (N = 7010, β = 0.0091, p < 2 × 10-16), and in two longitudinal cohort studies, the Lothian Birth Cohorts of 1921 (N = 430, β = 0.033, p = 7.9 × 10-4) and 1936 (N = 898, β = 0.0079, p = 0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, body mass index (BMI), smoking, and batch effects. In Generation Scotland, the increase in epigenetic outlier burden with age was not purely an artefact of an increase in DNA methylation level variability with age (epigenetic drift). Log10-transformed DNA methylation outlier burden in Generation Scotland was not related to self-reported, or family history of, age-related diseases, and it was not heritable (SNP-based heritability of 4.4%, p = 0.18). Finally, DNA methylation outlier burden was not significantly related to survival in either of the Lothian Birth Cohorts individually or in the meta-analysis after correction for multiple testing (HRmeta = 1.12; 95% CImeta = [1.02; 1.21]; pmeta = 0.021).ConclusionsThese findings suggest that, while it does not associate with ageing-related health outcomes, DNA methylation outlier burden does track chronological ageing and may also relate to survival. DNA methylation outlier burden may thus be useful as a marker of biological ageing.
| S-EPMC7098133 | biostudies-literature
Project description:The repeatability of longitudinal measures of whole blood DNA methylation (obtained using the Illumina 450k chip) was assessed in two cohorts of ageing. The Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936. Data were collected at ages 70, 73, and 76 (LBC1936) and 79, 87, 90 (LBC1921) with 478 participants having two or more measures of methylation.
| EGAS00001000910 | EGA
Project description:Elevated serum and cerebrospinal fluid concentrations of S100?, a protein predominantly found in glia, are associated with intracranial injury and neurodegeneration, although concentrations are also influenced by several other factors. The longitudinal association between serum S100? concentrations and brain health in nonpathological aging is unknown. In a large group (baseline N = 593; longitudinal N = 414) of community-dwelling older adults at ages 73 and 76 years, we examined cross-sectional and parallel longitudinal changes between serum S100? and brain MRI parameters: white matter hyperintensities, perivascular space visibility, white matter fractional anisotropy and mean diffusivity (MD), global atrophy, and gray matter volume. Using bivariate change score structural equation models, correcting for age, sex, diabetes, and hypertension, higher S100? was cross-sectionally associated with poorer general fractional anisotropy (r = -0.150, p = 0.001), which was strongest in the anterior thalamic (r = -0.155, p < 0.001) and cingulum bundles (r = -0.111, p = 0.005), and survived false discovery rate correction. Longitudinally, there were no significant associations between changes in brain imaging parameters and S100? after false discovery rate correction. These data provide some weak evidence that S100? may be an informative biomarker of brain white matter aging.
| S-EPMC6075468 | biostudies-literature
Project description:BackgroundThe biological mechanisms underlying frailty in older people are poorly understood. There is some evidence to suggest that DNA methylation patterns may be altered in frail individuals.MethodsParticipants were 791 people aged 70 years from the Lothian Birth Cohort 1936. DNA methylation was measured in whole blood. Biological age was estimated using two measures of DNA methylation-based age acceleration-extrinsic and intrinsic epigenetic age acceleration. We carried out an epigenome-wide association study of physical frailty, as defined by the Fried phenotype. Multinomial logistic regression was used to calculate relative risk ratios for being physically frail or pre-frail according to epigenetic age acceleration.ResultsThere was a single significant (P?=?1.16?×?10-7) association in the epigenome-wide association study comparing frail versus not frail. The same CpG was not significant when comparing pre-frail versus not frail. Greater extrinsic epigenetic age acceleration was associated with an increased risk of being physically frail, but not of being pre-frail. For a year increase in extrinsic epigenetic age acceleration, age- and sex-adjusted relative risk ratios (95% CI) for being physically frail or pre-frail were 1.06 (1.02, 1.10) and 1.02 (1.00, 1.04), respectively. After further adjustment for smoking and chronic disease, the association with physical frailty remained significant. Intrinsic epigenetic age acceleration was not associated with physical frailty status.ConclusionsPeople who are biologically older, as indexed by greater extrinsic epigenetic age acceleration, are more likely to be physically frail. Future research will need to investigate whether epigenetic age acceleration plays a causal role in the onset of physical frailty.
| S-EPMC6091041 | biostudies-literature
Project description:ObjectivesLoneliness is associated with poorer cognitive function in old age; however, the direction of this association is unknown. We tested for reciprocal associations between loneliness and the cognitive ability domains of processing speed, visuospatial ability, verbal memory, and crystallized ability.MethodWe used three triennial waves of longitudinal data from the Lothian Birth Cohort Study 1936, and tested for cross-lagged associations between loneliness and cognitive abilities using cross-lagged panel models.ResultsBetter processing speed, visuospatial ability, or crystallized ability at age 73, was associated with less positive changes in loneliness between ages 73 and 76; however, these associations were not replicated between ages 76 and 79. Loneliness at ages 73 and 76 did not predict subsequent changes in cognitive abilities.DiscussionOur findings indicate an association between cognitive ability and loneliness, such that individuals with lower cognitive abilities at age 73 may be at a slightly higher risk of becoming lonely. However, we did not find support for the hypothesis that loneliness causes a decline in cognitive health.
| S-EPMC6777773 | biostudies-literature
Project description:Hearing impairment is associated with poorer cognitive function in later life. We tested for the potential contribution of childhood cognitive ability to this relationship. Childhood cognitive ability is strongly related to cognitive function in older age, and may be related to auditory function through its association with hearing impairment risk factors. Using data from the Lothian Birth Cohort, 1936, we tested whether childhood cognitive ability predicted later-life hearing ability then whether this association was mediated by demographic or health differences. We found that childhood cognitive ability was negatively associated with hearing impairment risk at age 76 (odds ratio = .834, p = .042). However, this association was nonsignificant after subsequent adjustment for potentially mediating demographic and health factors. Next, we tested whether associations observed in older age between hearing impairment and general cognitive ability level or change were accounted for by childhood cognitive ability. At age 76, in the minimally adjusted model, hearing impairment was associated with poorer general cognitive ability level (? = -.119, p = .030) but was not related to decline in general cognitive ability. The former association became nonsignificant after additional adjustment for childhood cognitive ability (? = -.068, p = .426) suggesting that childhood cognitive ability contributes (potentially via demographic and health differences) to the association between levels of hearing and cognitive function in older age. Further work is needed to test whether early life cognitive ability also contributes to the association (documented in previous studies) between older-age hearing impairment and cognitive decline. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
| S-EPMC6742482 | biostudies-literature
Project description:AimAlcohol consumption during pregnancy is sometimes associated with adverse outcomes in offspring, potentially mediated by epigenetic modifications. We aimed to investigate genome-wide DNA methylation in cord blood of newborns exposed to alcohol in utero.Materials & methodsWe meta-analyzed information from six population-based birth cohorts within the Pregnancy and Childhood Epigenetics consortium.ResultsWe found no strong evidence of association at either individual CpGs or across larger regions of the genome.ConclusionOur findings suggest no association between maternal alcohol consumption and offspring cord blood DNA methylation. This is in stark contrast to the multiple strong associations previous studies have found for maternal smoking, which is similarly socially patterned. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure, exploration of a different tissue and a more global assessment of genomic DNA methylation might show evidence of association.
| S-EPMC5753623 | biostudies-literature
Project description:Gestational age (GA) and birth weight have been implicated in the determination of long-term health. It has been hypothesized that changes in DNA methylation may mediate these long-term effects. We obtained DNA methylation profiles from cord blood and peripheral blood at ages 7 and 17 in the same children from the Avon Longitudinal Study of Parents and Children. Repeated-measures data were used to investigate changes in birth-related methylation during childhood and adolescence. Ten developmental phenotypes (e.g. height) were analysed to identify possible mediation of health effects by DNA methylation. In cord blood, methylation at 224 CpG sites was found to be associated with GA and 23 CpG sites with birth weight. Methylation changed in the majority of these sites over time, but neither birth characteristic was strongly associated with methylation at age 7 or 17 (using a conservative correction for multiple testing of P < 1.03 × 10(-7)), suggesting resolution of differential methylation by early childhood. Associations were observed between birth weight-associated CpG sites and phenotypic characteristics in childhood. One strong association involved birth weight, methylation of a CpG site proximal to the NFIX locus and bone mineral density at age 17. Analysis of serial methylation from birth to adolescence provided evidence for a lack of persistence of methylation differences beyond early childhood. Sites associated with birth weight were linked to developmental genes and have methylation levels which are associated with developmental phenotypes. Replication and interrogation of causal relationships are needed to substantiate whether methylation differences at birth influence the association between birth weight and development.
| S-EPMC4459393 | biostudies-literature
Project description:BackgroundThe relationship between obesity and adverse health is well established, but little is known about the contribution of DNA methylation to obesity-related health outcomes. This study tests associations between an epigenetic score for body mass index (BMI) and health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian Birth Cohort 1936. This study also tests whether these associations are independent of phenotypic BMI.MethodAnalyses were conducted using data from the Lothian Birth Cohort 1936 (n?=?892). Weights for the epigenetic BMI score were derived using penalised regression on methylation data from unrelated Generation Scotland participants (n?=?2562). Associations were tested for replication in an independent sample: the Lothian Birth Cohort 1921 (n?=?433).ResultsA higher epigenetic BMI score was associated with higher BMI (R2?=?0.1), greater body weight (R2?=?0.06), greater time taken to walk 6?m, poorer lung function and poorer general physical health (all R2?=?0.02), greater levels of triglycerides (R2?=?0.09), greater %total HbA1c (R2?=?0.06), lower levels of high-density lipoprotein cholesterol (HDL; R2?=?0.08), higher HDL ratio (HDL/total cholesterol; R2 = 0.03), lower health-related quality of life, physical inactivity, and greater social deprivation (all R2?=?0.02). The epigenetic BMI score (per SD) was also associated with type 2 diabetes (OR 2.17, 95% CI 1.67, 2.84), cardiovascular disease (OR 1.45, 95% CI 1.24, 1.71) and high blood pressure (OR 1.30, 95% CI 1.13, 1.49; all p?<?0.00026 after Bonferroni correction). Associations were replicated for BMI (R2?=?0.06), body weight (R2?=?0.04), health-related quality of life (R2?=?0.02), HbA1c (R2?=?0.07) and triglycerides (R2?=?0.07; all p?<?0.0045 after Bonferroni correction).ConclusionsWe observed and replicated associations between an epigenetic score for BMI and variables related to poor physical health and metabolic syndrome. Regression models with both epigenetic and phenotypic BMI scores as predictors accounted for a greater proportion of variance in all outcome variables than either predictor alone, demonstrating independent and additive effects of epigenetic and phenotypic BMI scores.
| S-EPMC6760607 | biostudies-literature