scholarly journals DNA methylation outlier burden, health and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936

2019 ◽  
Author(s):  
Anne Seeboth ◽  
Daniel L. McCartney ◽  
Yunzhang Wang ◽  
Robert F. Hillary ◽  
Anna J. Stevenson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Meta Analysis ◽  
Family Health ◽  
Small Samples ◽  
Health Study ◽  
Birth Cohorts ◽  
Cross Sectional ◽  
Age Related ◽  
Potential Marker ◽  
Generation Scotland

AbstractDNA 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. Here, 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=7,010, 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=7.9×10−3, p=0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, 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 but it was in a meta-analysis (HRmeta=1.12; 95%CImeta=[1.02; 1.21]; pmeta=0.021). These 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.

scholarly journals Cohort profile for the STratifying Resilience and Depression Longitudinally (STRADL) study: A depression-focused investigation of Generation Scotland, using detailed clinical, cognitive, and neuroimaging assessments

2021 ◽  
Vol 4 ◽  
pp. 185
Author(s):  
Tina Habota ◽  
Anca-Larisa Sandu ◽  
Gordon D. Waiter ◽  
Christopher J. McNeil ◽  
J. Douglas Steele ◽  
...  
Keyword(s):  
Psychological Health ◽  
Early Life ◽  
Brain Magnetic Resonance Imaging ◽  
Family Health ◽  
Population Based ◽  
Health Study ◽  
Psychological Resilience ◽  
Birth Cohorts ◽  
Early Life Adversity ◽  
Generation Scotland

STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS provides an important opportunity to study complex gene-environment interactions, incorporating linkage to existing datasets and inclusion of early-life variables for two longitudinal birth cohorts. Specifically, data collection in STRADL included: socio-economic and lifestyle variables; physical measures; questionnaire data that assesses resilience, early-life adversity, personality, psychological health, and lifetime history of mood disorder; laboratory samples; cognitive tests; and brain magnetic resonance imaging. Some of the questionnaire and cognitive data were first assessed at the GS:SFHS baseline assessment between 2006-2011, thus providing longitudinal measures relevant to the study of depression, psychological resilience, and cognition. In addition, routinely collected historic NHS data and early-life variables are linked to STRADL data, further providing opportunities for longitudinal analysis. Recruitment has been completed and we consented and tested 1,188 participants.

scholarly journals Cohort profile for the STratifying Resilience and Depression Longitudinally (STRADL) study: A depression-focused investigation of Generation Scotland, using detailed clinical, cognitive, and neuroimaging assessments

2019 ◽  
Vol 4 ◽  
pp. 185 ◽  
Author(s):  
Tina Habota ◽  
Anca-Larisa Sandu ◽  
Gordon D. Waiter ◽  
Christopher J. McNeil ◽  
J. Douglas Steele ◽  
...  
Keyword(s):  
Psychological Health ◽  
Early Life ◽  
Brain Magnetic Resonance Imaging ◽  
Family Health ◽  
Population Based ◽  
Health Study ◽  
Birth Cohorts ◽  
Early Life Adversity ◽  
Generation Scotland ◽  
History Of

STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS provides an important opportunity to study complex gene-environment interactions, incorporating linkage to existing datasets and inclusion of early-life variables for two longitudinal birth cohorts. Specifically, data collection in STRADL included: socio-economic and lifestyle variables; physical measures; questionnaire data that assesses resilience, early-life adversity, personality, psychological health, and lifetime history of mood disorder; laboratory samples; cognitive tests; and brain magnetic resonance imaging. Some of the questionnaire and cognitive data were first assessed at the GS:SFHS baseline assessment between 2006-2011, thus providing longitudinal measures of depression and resilience. Similarly, routine NHS data and early-life variables are linked to STRADL data, further providing opportunities for longitudinal analysis. Recruitment has been completed and we consented and tested 1,188 participants.

1461-P: Cardiac Troponin T and Troponin I and Incident Diabetes in the General Population: Generation Scotland Scottish Family Health Study

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1461-P
Author(s):  
PAUL WELSH ◽  
DAVID PREISS ◽  
ARCHIE CAMPBELL ◽  
DAVID J. PORTEOUS ◽  
NICHOLAS L. MILLS ◽  
...  
Keyword(s):  
General Population ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Family Health ◽  
Incident Diabetes ◽  
Health Study ◽  
Cardiac Troponin T ◽  
Generation Scotland

Meta-analysis of the age-associated decline in maximal aerobic capacity in men: relation to training status

2000 ◽  
Vol 278 (3) ◽  
pp. H829-H834 ◽  
Author(s):  
Teresa M. Wilson ◽  
Hirofumi Tanaka
Keyword(s):  
Meta Analysis ◽  
Maximal Oxygen Consumption ◽  
Group Differences ◽  
Maximal Heart Rate ◽  
Maximal Aerobic Capacity ◽  
Cross Sectional ◽  
Physically Active ◽  
Age Related ◽  
Rate Of Decline ◽  
Exercise Status

Based on cross-sectional data, we recently reported that, in contrast to the prevailing view, the rate of decline in maximal oxygen consumption (V˙o 2 max) with age is greater in physically active compared with sedentary healthy women. We tested this hypothesis in men using a meta-analytic study ofV˙o 2 max values in the published literature. A total of 242 studies (538 subject groups and 13,828 subjects) met the inclusion criteria and were arbitrarily separated into sedentary (214 groups, 6,231 subjects), active (159 groups, 5,621 subjects), and endurance-trained (165 groups, 1,976 subjects) populations. Body fat percent increased with age in sedentary and active men ( P < 0.001), whereas no change was observed in endurance-trained men.V˙o 2 max was inversely and strongly related to age within each population ( r = −0.80 to −0.88, all P < 0.001) and was highest in endurance-trained and lowest in sedentary populations at any age. Absolute rates of decline inV˙o 2 max with age were not different ( P > 0.05) in sedentary (−4.0 ml ⋅ kg−1 ⋅ min−1 ⋅ decade−1), active (−4.0), and endurance-trained (−4.6) populations. Similarly, there were no group differences ( P > 0.05) in the relative (%) rates of decline inV˙o 2 max with advancing age (−8.7, −7.3, and −6.8%/decade, respectively). Maximal heart rate was inversely related to age within each population ( r = −0.88 to −0.93, all P < 0.001), but the rate of age-related reduction was not different among the populations. There was a significant decline in running mileage and speed with advancing age in the endurance-trained men. The present cross-sectional meta-analytic findings do not support the hypothesis that the rate of decline inV˙o 2 max with age is related to habitual aerobic exercise status in men.

scholarly journals Cadmium-associated differential methylation throughout the placental genome: epigenome-wide association study of two US birth cohorts

2017 ◽  
Author(s):  
Todd M. Everson ◽  
Tracy Punshon ◽  
Brian P. Jackson ◽  
Ke Hao ◽  
Luca Lambertini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Fetal Development ◽  
Meta Analysis ◽  
Reproductive Toxicity ◽  
Differential Methylation ◽  
Cellular Growth ◽  
Birth Cohorts ◽  
Inflammatory Signaling ◽  
P Values

AbstractBackgroundCadmium (Cd) is a ubiquitous toxicant that during pregnancy can impair fetal development. Cd sequesters in the placenta where it can impair placental function, impacting fetal development. We aimed to investigate Cd-associated variations in placental DNA methylation (DNAM), associations with gene expression, and identify novel pathways involved in Cd-associated reproductive toxicity.MethodsUsing placental DNAM and Cd concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the Rhode Island Child Health Study (RICHS, n=141), we performed an EWAS between Cd and DNAM, adjusting for tissue heterogeneity using a reference-free method. Cohort-specific results were aggregated via inverse variance weighted fixed effects meta-analysis, and variably methylated CpGs were associated with gene expression. We then performed functional enrichment analysis and tests for associations between gene expression and birth metrics.ResultsWe identified 17 Cd-associated differentially methylated CpG sites with meta-analysis p-values < 1e-05, two of which were within a 5% false discovery rate (FDR). Methylation levels at 9 of the 17 loci were associated with increased expression of 6 genes (5% FDR): TNFAIP2, EXOC3L4, GAS7, SREBF1, ACOT7, and RORA. Higher placental expression of TNFAIP2 and ACOT7, and lower expression of RORA, were associated with lower birth weight z-scores (p-values < 0.05).ConclusionCd associated differential DNAM and corresponding DNAM-expression associations at these loci are involved in inflammatory signaling and cell growth. The expression levels of genes involved in inflammatory signaling (TNFAIP2, ACOT7, and RORA), were also associated with birth metrics, suggesting a role for inflammatory processes in Cd-associated reproductive toxicity.SignificanceCadmium is a toxic environmental pollutant that can impair fetal development. The mechanisms underlying this toxicity are unclear, though disrupted placental functions could play an important role. In this study we examined associations between cadmium concentrations and DNA methylation throughout the placental genome, across two US birth cohorts. We observed cadmium-associated differential methylation, and corresponding methylation-expression associations at genes involved in cellular growth processes and/or immune and inflammatory signaling. This study provides supporting evidence that disrupted placental epigenetic regulation of cellular growth and immune/inflammatory signaling could play a role in cadmium associated reproductive toxicity in human pregnancies.

536. Cognitive Performance in Major Depressive Disorder in Generation Scotland: The Scottish Family Health Study (GS:SFHS)

2017 ◽  
Vol 81 (10) ◽  
pp. S217
Author(s):  
Joeri Meijsen ◽  
Archie Campbell ◽  
Andrew McIntosh ◽  
David Porteous ◽  
Ian Deary ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cognitive Performance ◽  
Family Health ◽  
Health Study ◽  
Major Depressive ◽  
Generation Scotland

scholarly journals Meta-analysis of genome-wide DNA methylation and integrative OMICs in human skeletal muscle

2020 ◽  
Author(s):  
S Voisin ◽  
M Jacques ◽  
S Landen ◽  
NR Harvey ◽  
LM Haupt ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Large Scale ◽  
Human Skeletal Muscle ◽  
Meta Analysis ◽  
Total N ◽  
Age Related ◽  
Differentially Methylated Genes ◽  
Comprehensive Picture ◽  
User Friendly

AbstractKnowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by aging in humans. Using a large-scale epigenome-wide association study (EWAS) meta-analysis of age in human skeletal muscle from 10 studies (total n = 908 human muscle methylomes), we identified 9,986 differentially methylated regions at a stringent false discovery rate < 0.005, spanning 8,748 unique genes, many of which related to skeletal muscle structure and development. We then integrated the DNA methylation results with known transcriptomic and proteomic age-related changes in skeletal muscle, and found that even though most differentially methylated genes are not altered at the mRNA or protein level, they are nonetheless strongly enriched for genes showing age-related differential expression. We provide here the most comprehensive picture of DNA methylation aging in human skeletal muscle, and have made our results available as an open-access, user-friendly, web-based tool called MetaMeth (https://sarah-voisin.shinyapps.io/MetaMeth/).

scholarly journals Generation Scotland - Using Electronic Health Records for Research

2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Archie Campbell ◽  
David Porteous
Keyword(s):  
Family Health ◽  
Health Study ◽  
Mortality Data ◽  
Generation Scotland ◽  
Scanned Images ◽  
Family Based ◽  
New Research ◽  
Lab Test ◽  
Longitudinal Dataset

Generation Scotland: Scottish Family Health Study (GS:SFHS) is a family-based genetic epidemiology study of ~24,000 volunteers from ~7000 families recruited across Scotland between 2006 and 2011 with the capacity for follow-up through record linkage and re-contact. Broad consent was obtained for linkage to “medical records” for 98% of the cohort. Participants completed a questionnaire, provided samples, and underwent clinical assessment. The samples and data collected form a resource with consent for research on the genetics of health, becoming a longitudinal dataset by linkage to routine NHS hospital, maternity, lab test, prescribing, dentistry and mortality data. Researchers can use the linked datasets to test research hypotheses on a stratified population and target recruitment to new studies. We have established and validated EHR linkage, overcoming technical and governance issues in the process. We plan to collaborate with UK Biobank, creating a combined cohort of over 50,000 people in Scotland, and using the SHARE register to obtain new research samples from routine NHS tests. We will extend linkage to include primary care data and scanned images in the next year. The resources are available to academic and commercial researchers through a managed access process.

scholarly journals Intelligence and neuroticism in relation to depression and psychological distress: evidence of interaction using data from Generation Scotland: Scottish Family Health Study and UK Biobank

2016 ◽  
Author(s):  
LB Navrady ◽  
SJ Ritchie ◽  
SWY Chan ◽  
DM Kerr ◽  
MJ Adams ◽  
...  
Keyword(s):  
Psychological Distress ◽  
Significant Interaction ◽  
Protective Factor ◽  
Short Form ◽  
Family Health ◽  
Population Based ◽  
Depressive Illness ◽  
Health Study ◽  
Uk Biobank ◽  
Generation Scotland

ABSTRACTBackgroundNeuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-relationships of neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined.MethodsAssociations and interactions between neuroticism and general intelligence (g) on MDD and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, N=19,200) and UK Biobank (N=90,529). The Eysenck Personality Scale Short Form-Revised measured neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS.ResultsNeuroticism was associated with MDD and psychological distress in both samples. A significant interaction between neuroticism and g in predicting MDD status was found in UK Biobank (OR = 0.96, p < .01), suggesting that higher g ameliorated the adverse effects of neuroticism on the likelihood of having MDD. This interaction was not found in GS:SFHS. In both samples, higher neuroticism and lower intelligence were associated with increased psychological distress. A significant interaction was also found in both cohorts (GS:SFHS: ß = -0.05, p < .01; UK Biobank: ß = -0.02, p < .01), such that intelligence protected against the deleterious effect of neuroticism on psychological distress.ConclusionsFrom two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of neuroticism on risk for depressive illness and psychological distress.

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