scholarly journals DNA methylation-based measures of accelerated biological ageing and the risk of dementia in the oldest-old: a study of the Lothian Birth Cohort 1921

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruth A. Sibbett ◽  
Drew M. Altschul ◽  
Riccardo E. Marioni ◽  
Ian J. Deary ◽  
John M. Starr ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Cohort ◽  
Oldest Old ◽  
Biological Ageing ◽  
Lothian Birth Cohort

scholarly journals Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

2019 ◽  
Author(s):  
Anna J. Stevenson ◽  
Daniel L. McCartney ◽  
Robert F. Hillary ◽  
Archie Campbell ◽  
Stewart W. Morris ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cognitive Ability ◽  
Chronic Inflammation ◽  
Birth Cohort ◽  
Large Scale ◽  
Acute Infection ◽  
Plasma Concentrations ◽  
Generation Scotland ◽  
Lothian Birth Cohort ◽  
Serum Crp

ABSTRACTResults from large cohort studies investigating the association between inflammation and cognition have been mixed, possibly due to methodological disparities. However, a key issue in research utilising inflammatory biomarkers is their typically phasic responses. C-reactive protein (CRP) is widely used to investigate the association between chronic inflammation and cognition, but its plasma concentrations can markedly deviate in response to acute infection. Recently a large-scale epigenome-wide association study identified DNA methylation correlates of CRP. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure. Here, we generate an epigenetic CRP score and investigate its trajectories with age, and associations with cognitive ability, in comparison to serum CRP in two cohorts: a longitudinal study of older adults (the Lothian Birth Cohort 1936, n=889) and a large, cross-sectional cohort (Generation Scotland, n=7,028).We identified differing trajectories of serum CRP across the cohorts, with no homogeneous trends seen with age. Conversely, the epigenetic score was consistently found to increase with age, and to do so more rapidly in males compared to females. Higher levels of serum CRP were found to associate with poorer cognition in Lothian Birth Cohort 1936, but not in Generation Scotland. However, a consistent negative association was identified between cognition and the epigenetic score in both cohorts. Furthermore, the epigenetic score accounted for a greater proportion of variance in cognitive ability.Our results suggest that epigenetic signatures of acute inflammatory markers may provide an enhanced signature of chronic inflammation, allowing for more reliable stratification of individuals, and thus clearer inference of associations with incident health outcomes.

scholarly journals An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort

2019 ◽  
Vol 43 (9) ◽  
pp. 1795-1802 ◽  
Author(s):  
Olivia K. L. Hamilton ◽  
Qian Zhang ◽  
Allan F. McRae ◽  
Rosie M. Walker ◽  
Stewart W. Morris ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Physical Health ◽  
Birth Cohort ◽  
Poor Physical Health ◽  
Major Disease ◽  
Lothian Birth Cohort

scholarly journals Epigenetic signatures of smoking associate with cognitive function, brain structure, and mental and physical health outcomes in the Lothian Birth Cohort 1936

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Janie Corley ◽  
Simon R. Cox ◽  
Sarah E. Harris ◽  
Maria Valdéz Hernandez ◽  
Susana Muñoz Maniega ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cognitive Function ◽  
Health Outcomes ◽  
Physical Health ◽  
Birth Cohort ◽  
Smoking Status ◽  
Brain Mri ◽  
Smoking Exposure ◽  
Eta Squared ◽  
Lothian Birth Cohort

Abstract Recent advances in genome-wide DNA methylation (DNAm) profiling for smoking behaviour have given rise to a new, molecular biomarker of smoking exposure. It is unclear whether a smoking-associated DNAm (epigenetic) score has predictive value for ageing-related health outcomes which is independent of contributions from self-reported (phenotypic) smoking measures. Blood DNA methylation levels were measured in 895 adults aged 70 years in the Lothian Birth Cohort 1936 (LBC1936) study using the Illumina 450K assay. A DNA methylation score based on 230 CpGs was used as a proxy for smoking exposure. Associations between smoking variables and health outcomes at age 70 were modelled using general linear modelling (ANCOVA) and logistic regression. Additional analyses of smoking with brain MRI measures at age 73 (n = 532) were performed. Smoking-DNAm scores were positively associated with self-reported smoking status (P < 0.001, eta-squared ɳ2 = 0.63) and smoking pack years (r = 0.69, P < 0.001). Higher smoking DNAm scores were associated with variables related to poorer cognitive function, structural brain integrity, physical health, and psychosocial health. Compared with phenotypic smoking, the methylation marker provided stronger associations with all of the cognitive function scores, especially visuospatial ability (P < 0.001, partial eta-squared ɳp2 = 0.022) and processing speed (P < 0.001, ɳp2 = 0.030); inflammatory markers (all P < 0.001, ranges from ɳp2 = 0.021 to 0.030); dietary patterns (healthy diet (P < 0.001, ɳp2 = 0.052) and traditional diet (P < 0.001, ɳp2 = 0.032); stroke (P = 0.006, OR 1.48, 95% CI 1.12, 1.96); mortality (P < 0.001, OR 1.59, 95% CI 1.42, 1.79), and at age 73; with MRI volumetric measures (all P < 0.001, ranges from ɳp2 = 0.030 to 0.052). Additionally, education was the most important life-course predictor of lifetime smoking tested. Our results suggest that a smoking-associated methylation biomarker typically explains a greater proportion of the variance in some smoking-related morbidities in older adults, than phenotypic measures of smoking exposure, with some of the accounted-for variance being independent of phenotypic smoking status.

scholarly journals DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian Birth Cohort 1936

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Catharine R. Gale ◽  
Riccardo E. Marioni ◽  
Sarah E. Harris ◽  
John M. Starr ◽  
Ian J. Deary
Keyword(s):  
Dna Methylation ◽  
Older People ◽  
Birth Cohort ◽  
Epigenetic Clock ◽  
Physical Frailty ◽  
Lothian Birth Cohort

scholarly journals An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort 1936

2018 ◽  
Author(s):  
Olivia KL Hamilton ◽  
Qian Zhang ◽  
Allan F McRae ◽  
Rosie M Walker ◽  
Stewart W Morris ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Physical Health ◽  
Birth Cohort ◽  
Body Mass ◽  
Social Deprivation ◽  
The Body ◽  
Poor Physical Health ◽  
Related Quality ◽  
Lothian Birth Cohort ◽  
Health Related

ABSTRACTBackgroundThe relationship between obesity and adverse health is well established, but little is known about the contribution of DNA methylation to obesity-related health outcomes. Additionally, it is of interest whether such contributions are independent of those attributed by the most widely used clinical measure of body mass – the Body Mass Index (BMI).MethodWe tested whether an epigenetic BMI score accounts for inter-individual variation in health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian Birth Cohort 1936 (n=903). Weights for the epigenetic BMI score were derived using penalised regression on methylation data from unrelated Generation Scotland participants (n=2566).ResultsThe Epigenetic BMI score was associated with variables related to poor physical health (R2 ranges from 0.02-0.10), metabolic syndrome (R2 ranges from 0.01-0.09), lower crystallised intelligence (R2=0.01), lower health-related quality of life (R2=0.02), physical inactivity (R2=0.02), and social deprivation (R2=0.02). The epigenetic BMI score (per SD) was also associated with self-reported type 2 diabetes (OR 2.25, 95 % CI 1.74, 2.94), cardiovascular disease (OR 1.44, 95 % CI 1.23, 1.69) and high blood pressure (OR 1.21, 95% CI 1.13, 1.48; all at p<0.0011 after Bonferroni correction).ConclusionsOur results show that regression models with epigenetic and phenotypic BMI scores as predictors account for a greater proportion of all outcome variables than either predictor alone, demonstrating independent and additive effects of epigenetic and phenotypic BMI scores.

scholarly journals Alzheimer’s Disease Susceptibility Genes APOE and TOMM40, and Hippocampal Volumes in the Lothian Birth Cohort 1936

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80513 ◽  
Author(s):  
Donald M. Lyall ◽  
Natalie A. Royle ◽  
Sarah E. Harris ◽  
Mark E. Bastin ◽  
Susana Muñoz Maniega ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Birth Cohort ◽  
Disease Susceptibility ◽  
Susceptibility Genes ◽  
Lothian Birth Cohort

scholarly journals Longitudinal Associations Between Loneliness and Cognitive Ability in the Lothian Birth Cohort 1936

2018 ◽  
Vol 74 (8) ◽  
pp. 1376-1386 ◽  
Author(s):  
Judith A Okely ◽  
Ian J Deary
Keyword(s):  
Cognitive Ability ◽  
Birth Cohort ◽  
Processing Speed ◽  
Verbal Memory ◽  
Cognitive Abilities ◽  
Birth Cohort Study ◽  
Visuospatial Ability ◽  
Lothian Birth Cohort ◽  
Longitudinal Associations ◽  
Reciprocal Associations

Abstract Objectives Loneliness 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. Method We 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. Results Better 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. Discussion Our 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.

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