Epigenetic responses to social and environmental cues in early life and over the life course: impact on healthy ageing in UK population-based cohorts

Lead Research Organisation: King's College London
Department Name: Genetics and Molecular Medicine

Abstract

Epigenetic mechanisms such as DNA methylation are key regulators of gene function. Epigenetic signals are malleable and can change in response to internal and external stimuli. The epigenome thereby provides a mechanism of interaction between the genome with the environment, and we hypothesize that early life stimuli and exposures over the life course leave an epigenetic mark.

The proposal will explore DNA methylation in 4,024 samples from four British cohort studies (the MRC National Survey for Health and Development (NSHD) or 1946 birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK)) in order to identify epigenetic signatures of early life experience and exposure to social, environmental, and biological stimuli over the life course, linking findings to changes in physical and cognitive function during ageing. Each study captures a range of early life experiences, longitudinal health measures and lifestyle questionnaire data from adult life, DNA samples collected at single or multiple time-points, and in a sample subset, multiple genomic data for follow-up analyses.

The primary research design is a prospective analysis of longitudinal data across 2,336 blood and 1,688 buccal samples from the four cohorts. The first aim of the research will be to establish whether biological, environmental, and social stimuli in early life and over the life course result in detectable differences in DNA methylation profiles in adults. We will consider whether there are epigenetic associations with a number of factors including biological, environmental and social factors in utero and in early childhood (e.g. birthweight, childhood growth, maternal smoking during pregnancy, nutrition, parental socioeconomic position), and in later life: (e.g. smoking, alcohol consumption, physical activity, diet, stressful events, adult socioeconomic position). The second aim is to assess whether there are differences between cohorts in DNA methylation patterns, comparing samples containing individuals born in different years (1946, 1958 and 1970), accounting for age, since these may reflect differences between cohorts in environmental and social influences in early life.

Our third aim is to explore the role of epigenetics in healthy functional ageing by applying a two-fold approach. First, we will compare epigenetic signatures to longitudinal functional health trajectories throughout life across cohorts, across cell types (blood and buccal), and across different age categories. We will explore whether DNA methylation signatures of early life experiences can mediate functional ageing trajectories (such as cardiovascular, lung and cognitive function), and whether they can be reversed in response to social and environmental exposures in later life. Our fourth aim is to apply a new approach to estimate biological age, the epigenetic clock, to assess the rate of epigenetic ageing and relate it to early life stimuli and longitudinal biomedical, social, and environmental trajectories.

Additional analyses in subsamples will include DNA methylation profiling at multiple time-points to estimate reversibility of DNA methylation, cross-tissue comparison across blood, buccal, and additional tissues, and gene expression analysis for functional interpretation. Replication will be pursued in 3,970 samples from four independent UK-population-based cohorts.

The findings will establish the feasibility of our approach by combining modest samples of participants across each of the four cohorts into a large sample well powered to determine the influence of early life factors on epigenetic signatures throughout the life course. The proof of concept approach will allow such analyses to be extended to larger samples within cohorts by forming the basis for further funding applications and establishing an epigenetic research network across UK population-based cohorts.

Planned Impact

Human epigenetics is a relatively recent research field and its potential for understanding the pathways linking early experience and later life health, and its clinical, public health and societal relevance is yet to be fully understood. Given this context, impacts are expected on a diverse range of major beneficiaries:

1. Academics from the wider research community, as described in the Academic Beneficiaries section will benefit from:
- The generation of new knowledge related to early life impacts on epigenetics and functional ageing trajectories
- The generation of new datasets to enhance these unique cohorts and integrate with available 'omic data for further exploration by other researchers
- The aggregation through collaboration of additional expertise in this area
- Training of early career researchers in the specific areas, and development of cross-disciplinary expertise.

2. The public sector.
The results of the research will be useful to practitioners working in health education and public health, their regulators, and professional associations. The research also has translational potential of the findings to health management. Translatable findings will include results on reversibility, which will highlight modifiable pathways to stop or reverse degenerative ageing processes by implementing lifestyle changes and more effective strategies for health management. For example, identification of specific methylation changes may help identify new underlying biological mechanisms that link early life exposures to later ageing phenotypes and hence inform new preventative and treatment strategies.

3. The general public.
Findings from the research will be relevant to issues in everyday life, such as parenting, physical and mental health. Translatable findings may include results on reversibility, which may highlight modifiable pathways to stop or reverse degenerative ageing processes by implementing lifestyle changes and more effective strategies for health management.

4. Industry.
Biotechnology companies may be able to exploit the improved biological knowledge that will be generated to develop novel products and services.

Economic and social benefits will be manifest through:
- Improved effectiveness of public services if the new biological insights result in better ways of predicting, treating and preventing functional decline with ageing (by implementing lifestyle changes and more effective strategies for health management, novel treatments, better diagnostics);
- Economic benefits to biotechnology companies able to exploit actionable translational opportunities with respect to the development of novel prognostic and therapeutic approaches that build on the associations we detect;
- Benefits to those developing and marketing omics assays, in terms of defining additional content, and expanding markets;
- Maximising value of omics data collected within systems such as the NHS for other purposes, by augmenting the value of such data for healthy ageing;
- Improved health outcomes if the work leads to potential clinical translation, resulting in further personal, social and economic benefits.

All of the cohorts have an excellent track record in raising awareness of cohort study findings among the public and policy makers (including central, local, and devolved administrations), primarily through media and targeted events, and findings from this work will be communicated to these audience through non-technical briefings and accompanying press releases. The resources for dissemination being developed by the CLOSER project (www.closer.ac.uk) will be used to improve the dissemination of findings to a wide range of beneficiaries
 
Description The project formally commenced in October 2015. Epigenetic signatures were profiled in samples from four UK population-based cohorts using the Illumina Infinium MethylationEPIC BeadChip which assays DNA methylation levels at 850,000 sites across the genome. The newly-generated epigenetic profiles were compared to factors that capture exposure to social, environmental, and biological stimuli over the life course, within and across cohorts. Furthermore, estimates of the rate of epigenetic ageing were also obtained, and both epigenetic variation and epigenetic ageing rates were compared to functional health outcomes and trajectories in later life. Overall, the key findings from this project identified an ageing signature in the human epigenome and links between epigenetic variation and functional health outcomes in later life.

The workload covered the four major objectives of the grant. A significant period of time was needed to obtain access to phenotype data from each cohort. Following data access, a major component of the workflow focused on harmonising phenotype data across cohorts, including specifically data that captured exposure to social, environmental, and biological stimuli over the life course. Access to biological samples was time-efficient and epigenetic profiling was carried out smoothly in two batches within the same genome centre. The analytical workflow focused on comparing epigenetic profiles within and across cohorts with respect to harmonised phenotype data.

The key significant findings for each Aim are summarised as follows:
Aim 1. To identify epigenetic signatures of early life experience and exposure to social, environmental, and biological stimuli over the life course, within and across cohorts. Epigenetic signatures were detected for several biological and environmental stimuli over the life course, including strong signatures of chronological age and smoking, as well as yet unpublished work on epigenetic variation related to obesity and menopause-related traits.
Aim 2. To establish whether cohort differences in environments and social circumstances are reflected in epigenetic signals. Changes in epigenetic signals were observed with respect to decade of birth.
Aim 3. To investigate the impact of epigenetics on functional ageing trajectories. Epigenetic variation was compared to cross-sectional and longitudinal phenotype data for age-related traits. Although, the majority of phenotypes tested were not significantly associated with epigenetic profiles, multiple significant signals were obtained for metabolic health, including obesity.
Aim 4. To profile the rate of epigenetic ageing, identify early life predictors, and associations with functional health outcomes in later life. The rate of epigenetic ageing was successfully profiled across cohorts and these variables were compared to multiple factors and health outcomes. Significant variance in epigenetic ageing was observed with respect to decade of birth, but there were no significant links with functional ageing trajectories or health outcomes in later life.
Exploitation Route We envisage that the research findings will have scientific and broader societal and economic impacts. Academic routes to take the findings further include follow-up research work through new collaborations that were established through the grant. The project allowed us to form a new multi-disciplinary research network combining expertise in complementary fields, which has led to new collaborative projects. As an example, part of the research team participated in new research funding applications, and are now recipients of NIA and MRC grants awarded to explore biomedical data from the 1958 cohort participants at age 60. As part of the grant dissemination activities we presented the research findings at national and international conferences, and hosted the second meeting of the Epigenetics in Social Sciences Network, which has now grown to include over 30 members and into a yearly event, generating further collaborations. The grant supported postdoctoral fellows who have moved to further career opportunities in academia, including group leader and advanced-level postdoctoral associate positions. Our findings are also helpful to other researchers in the academic sector who study the molecular basis of ageing and impacts of smoking. The results may be of interest to the public sector and healthcare, in terms of informing healthcare policies and implementing lifestyle changes that may influence the rate of ageing and age-related molecular changes.
Sectors Communities and Social Services/Policy

Education

Healthcare

Pharmaceuticals and Medical Biotechnology

 
Description Human epigenetics is a relatively recent research field and its potential for understanding the pathways linking early experience and later life health, and its clinical, public health and societal relevance is yet to be fully understood. Potential impacts were expected on a diverse range of major beneficiaries, including academics from the wider research community, the public sector, the general public, and industry. To date, the results from this research have contributed towards 20 academic journal publications and 17 dissemination events, primarily targeting academic audiences. Although to date the results from this research have contributed predominantly towards the academic sector, we have also made some impacts to non-academic beneficiaries in several ways. First, we helped set up and are part of the Epigenetics in the Social Sciences Network (ESSN; http://www.bristol.ac.uk/integrative-epidemiology/ epigenetics-social-science-network/), which is a collaborative network of academic researchers working on epigenetics in social sciences. Second, we organised an ESRC-epigenetics funded research network meeting in June 2017 to disseminate the results of the grants to researchers across both the academic and public and industry sectors. This full day meeting was well attended with approximately 35 international attendees - predominantly from academia, but also some from the public sector (e.g. research councils) and industry. We also attended related and follow-up meetings at the University of Bristol, at the University of Durham, and in London. Third, we published a systematic review (Maddock et al. 2018) on the associations between body size, nutrition and socioeconomic position in early life and the epigenome. Fourth, we have been engaged in disseminating the results from our research not only to academic audiences, but also to industry (e.g. talk at industry-organised events such as the EMBL-EBI Industry Workshop 'Epigenetics for ageing and disease' in 2018), and have explored other approaches and challenges to broaden the impacts of our research to the other expected beneficiaries, including public sector and industry. Furthermore, the cohorts included in this grant have an excellent track record in raising awareness of cohort study findings among the public and policy makers (including central, local, and devolved administrations), primarily through media and targeted events, and findings from this work will be communicated to these audience through non-technical briefings and accompanying press releases. The resources for dissemination being developed by the CLOSER project (www.closer.ac.uk) will be used to improve the dissemination of findings to a wide range of beneficiaries.
Sector Education,Environment,Healthcare
Impact Types Societal

 
Description Expert Witness to the Science and Technology Committee of the House of Lords for its inquiry on "Ageing: Science, Technology and Healthy Living", London, UK.
Geographic Reach National 
Policy Influence Type Contribution to a national consultation/review
URL https://committees.parliament.uk/oralevidence/35/html/
 
Description We have published a systematic review protocol: Maddock J, Wulaningsih W, Hardy R. (2017). Impact of body size, nutrition and socioeconomic position in early life on the epigenome: a systematic review protocol.. Systematic reviews, 6 (1), pp. 129
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
 
Description We have published a systematic review: Maddock J, Wulaningsih W, Castillo Fernandez J, Wong A, Ploubidis G, Goodman A, Bell J, Kuh D, Hardy R. Associations between body size, nutrition and socioeconomic position in early life and the epigenome: A systematic review. PLoS ONE 13(8):e0201672, https://doi.org/10.1371/journal.pone.0201672
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Biomedical follow-up of 1958 Birth Cohort Study members at age 60
Amount £1,942,690 (GBP)
Funding ID MR/P023444/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 12/2021
 
Description HDHL DIMENSION: Dietary induced methylome and transcriptome dynamics assessing nutrition impacts on cardiovascular and metabolic health
Amount £267,767 (GBP)
Funding ID BB/S020845/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 03/2019 
End 03/2022
 
Description Healthy transitions from mid-life to early older age: biomedical follow-up of 1958 Birth Cohort Study members at age 60
Amount $499,806 (USD)
Funding ID AG052519-01 
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 08/2016 
End 08/2017
 
Description Healthy transitions from mid-life to early older age: biomedical follow-up of 1958 Birth Cohort Study members at age 60
Amount $324,438 (USD)
Funding ID 1R01AG052519-01A1 
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 08/2017 
End 05/2022
 
Description Identification of regulatory genomic networks underlying skin ageing
Amount £110,026 (GBP)
Funding ID BB/V509656/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2020 
End 09/2024
 
Title Additional file 1: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S1. Linear regression model describing summary statistics for the association between blood methylation at cg21245277 and gingival bleeding. (CSV 5 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_1_of_Epigenetic_findings_in_per...
 
Title Additional file 1: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S1. Linear regression model describing summary statistics for the association between blood methylation at cg21245277 and gingival bleeding. (CSV 5 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_1_of_Epigenetic_findings_in_per...
 
Title Additional file 2 of Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects 
Description Additional file 2: Table S1. Statistically significant CpGs in relation to current versus never smoking status at false discovery rate (FDR) 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Novel_DNA_methylation_sign...
 
Title Additional file 2 of Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects 
Description Additional file 2: Table S1. Statistically significant CpGs in relation to current versus never smoking status at false discovery rate (FDR) 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Novel_DNA_methylation_sign...
 
Title Additional file 2: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S2. Linear regression model describing summary statistics for the association between blood methylation at cg08157914 and tooth mobility. (CSV 5 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Epigenetic_findings_in_per...
 
Title Additional file 2: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S2. Linear regression model describing summary statistics for the association between blood methylation at cg08157914 and tooth mobility. (CSV 5 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Epigenetic_findings_in_per...
 
Title Additional file 2: of Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 
Description Table S1. Four smoking-induced differentially methylated and expressed genes in blood samples. Table S2. Validation of 14 tissue-shared smoking-DMS across four sample types. Table S3. Replication of the 42 smoking-DMS in the LEAP cohort [39] with 104 current smokers and non-smokers. Table S4. Previously-identified smoking genetic variants and their impacts on DNA methylation and gene expression in adipose tissue. Table S5. DNA methylation QTL (meQTLs) analyses at the chromosome 19 region from Loukola et al. [43], showing replication in TwinsUK adipose tissue samples. Table S6. Characteristics of TwinsUK (adipose tissue, blood samples, and skin tissue [34]), Finnish cohort [74, 75], LEAP cohort [39], and lung cancer [76] samples. (XLSX 43 kb) 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Smoking_induces_coordinate...
 
Title Additional file 2: of Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 
Description Table S1. Four smoking-induced differentially methylated and expressed genes in blood samples. Table S2. Validation of 14 tissue-shared smoking-DMS across four sample types. Table S3. Replication of the 42 smoking-DMS in the LEAP cohort [39] with 104 current smokers and non-smokers. Table S4. Previously-identified smoking genetic variants and their impacts on DNA methylation and gene expression in adipose tissue. Table S5. DNA methylation QTL (meQTLs) analyses at the chromosome 19 region from Loukola et al. [43], showing replication in TwinsUK adipose tissue samples. Table S6. Characteristics of TwinsUK (adipose tissue, blood samples, and skin tissue [34]), Finnish cohort [74, 75], LEAP cohort [39], and lung cancer [76] samples. (XLSX 43 kb) 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Smoking_induces_coordinate...
 
Title Additional file 3: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S3. Linear regression model describing summary statistics for the association between blood methylation at cg11051055 and tooth mobility. (CSV 5 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_3_of_Epigenetic_findings_in_per...
 
Title Additional file 3: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S3. Linear regression model describing summary statistics for the association between blood methylation at cg11051055 and tooth mobility. (CSV 5 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_3_of_Epigenetic_findings_in_per...
 
Title Additional file 4: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S4. Covariate data and methylation beta values at cg21245277 in blood (CSV 91 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_4_of_Epigenetic_findings_in_per...
 
Title Additional file 4: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S4. Covariate data and methylation beta values at cg21245277 in blood (CSV 91 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_4_of_Epigenetic_findings_in_per...
 
Title Additional file 5: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S5. Covariate data and methylation beta values at 58 tooth mobility significant CpG sites in blood. (CSV 410 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_5_of_Epigenetic_findings_in_per...
 
Title Additional file 5: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S5. Covariate data and methylation beta values at 58 tooth mobility significant CpG sites in blood. (CSV 410 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_5_of_Epigenetic_findings_in_per...
 
Title Additional file 6: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S6. Covariate data, gingival bleeding, and methylation beta values at 247 CpG-sites in blood. (CSV 1595 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_6_of_Epigenetic_findings_in_per...
 
Title Additional file 6: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S6. Covariate data, gingival bleeding, and methylation beta values at 247 CpG-sites in blood. (CSV 1595 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_6_of_Epigenetic_findings_in_per...
 
Title Additional file 7: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S7. Covariate data, tooth mobility, and methylation beta values at 247 CpG sites in blood. (CSV 1486 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_7_of_Epigenetic_findings_in_per...
 
Title Additional file 7: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S7. Covariate data, tooth mobility, and methylation beta values at 247 CpG sites in blood. (CSV 1486 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_7_of_Epigenetic_findings_in_per...
 
Title Additional file 8: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S8. Covariate data, tooth mobility, gingival bleeding, and methylation beta values at 248 CpG sites in buccal tissue for all subjects. (CSV 152 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_8_of_Epigenetic_findings_in_per...
 
Title Additional file 8: of Epigenetic findings in periodontitis in UK twins: a cross-sectional study 
Description Table S8. Covariate data, tooth mobility, gingival bleeding, and methylation beta values at 248 CpG sites in buccal tissue for all subjects. (CSV 152 kb) 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Additional_file_8_of_Epigenetic_findings_in_per...
 
Title DNA methylation Illumina-EPIC datasets in UK population-based cohorts 
Description As part of the ESRC-funded epigenetics grant we have generated four large-scale epigenetic datasets from the TwinsUK cohort, from the NSHD (1946 birth cohort), from the NCDS cohort (1958 birth cohort), and from the 1970 birth cohort. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact We generated genome-wide DNA methylation datasets in samples from 4 UK population-based cohorts. The datasets are in samples from the TwinsUK cohort, the NSHD cohort (1946 birth cohort), the NCDS cohort (1958 birth cohort), and from the 1970 birth cohort (BC70). The datasets are now available in the public domain through the following identifiers: (i) TwinsUK data are uploaded on the ReShare UK Data Service, under Data collection id 853526; (ii) NSHD data access is through DOI 10.5522/NSHD/S202; (iii) NCDS and BCS70 data access is through DOI http://doi.org/10.5255/UKDA-SN-5594-2 . The first immediate benefit of these data will be to the academic community in terms of providing large-scale methylome data for researchers in epigenetics to explore in the context of their own research hypotheses. Indeed, independent bona-fide researchers are already undertaking independent research efforts based on some of these datasets, for example see 
 
Title Supplementary information files for Life course socioeconomic position and DNA methylation age acceleration in mid-life 
Description Supplementary files for article Life course socioeconomic position and DNA methylation age acceleration in mid-life Background: Ageing biomarkers can help us better understand how well-established socioeconomic position (SEP) disparities in ageing occur. A promising new set of DNAm methylation (DNAm)-based ageing biomarkers indicate through their age acceleration (AA) measures if biological ageing is slower or faster than chronological ageing. Few studies have investigated the association between SEP and DNAm AA. Methods: We used linear regression to examine the sex-adjusted relationships between childhood social class, adult social class, intergenerational social class change, education and adult household earnings with first (Horvath AA and Hannum AA) and second generation (PhenoAge AA and GrimAge AA) DNAm AA markers using data from the MRC National Survey of Health and Development. Results: In the first-generation biomarkers, there was little evidence of any associations with Horvath AA but associations of childhood social class and income with Hannum AA were observed. Strong associations were seen between greater disadvantage in childhood and adult SEP and greater AA in the second generation biomarkers. For example, those with fathers in an unskilled occupational social class in childhood had 3.6 years greater PhenoAge AA (95% CI 1.8 to 5.4) than those with fathers from a professional social class. Individuals without qualifications had higher AA compared with those with higher education (4.1 years greater GrimAge AA (95% CI 3.1 to 5.0)). Conclusion: Our findings highlight the importance of exposure to social disadvantage in childhood to the biological ageing process. The second generation clocks appear to be more sensitive to the accumulation of social disadvantage across the life course. 
Type Of Material Database/Collection of data 
Year Produced 2023 
Provided To Others? Yes  
URL https://repository.lboro.ac.uk/articles/dataset/Supplementary_information_files_for_Life_course_soci...
 
Description Additional epigenetic studies in 1958BC in collaboration with UCL 
Organisation University College London
Department Centre for Longitudinal Studies
Country United Kingdom 
Sector Academic/University 
PI Contribution Further collaborative work between Dr Bell at KCL and Prof Ploubidis and Prof Goodman at UCL has resulted in securing additional funding (to Prof Goodman) to carry out epigenetic profiling in additional samples from the 1958BC. This has now been approved and work is underway to proceed with epigenetic profiling. A related follow-up collaborative output directly resulting from this grant was to include Dr Bell as a co-investigator on two NIA-funded and MRC-funded awards led by UCL (PI: Goodman) for a biomedical follow up of 1958 birth cohort participants at age 60. The long-term aim would be to profile longitudinal epigenomics in a sample of individuals form the 1958BC to study the role of different exposures on the epigenome and with respect to ageing outcomes. Lastly, we also reached a bi-lateral agreement to collaborate on 1958BC cohort epigenetic data analysis with researchers leading the E4: Intestella ESRC-epigenetics funded grant, specifically Prof Caroline Relton, Prof Chris Power, and Dr Matt Suderman. Collaborative projects so far led by our group focus on ageing and functional capacity.
Collaborator Contribution Prof Goodman leads two NIA-funded and MRC-funded bids for a biomedical follow up of 1958 birth cohort participants at age 60. The long-term aim would be to profile longitudinal epigenomics in a sample of individuals form the 1958BC to study the role of different exposures on the epigenome and with respect to ageing outcomes. Prof Goodman, in collaboration with Dr Bell and Dr Ploubidis secured funding to perform epigenetic profiling in additional samples from the 1958BC at age 44-45. Work is underway to proceed with sample selection and epigenetic profiling, which will be performed in collaboration with Dr Bell. A bi-lateral agreement to collaborate on 1958BC cohort epigenetic data analysis with researchers leading the E4: Intestella ESRC-epigenetics funded grant, specifically Prof Caroline Relton, Prof Chris Power, and Dr Matt Suderman. Collaborative projects so far led by the Bristol group focus on early life adversity and epigenetics.
Impact NIA and MRC grants have been awarded (see Further funding section). Sample selection is underway, but work on the additional epigenetic profiling has not yet started.
Start Year 2017
 
Description Additional epigenetic studies in 1958BC in collaboration with the University of Bristol 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution We reached a bi-lateral agreement to collaborate on 1958BC cohort epigenetic data analysis with researchers leading the E4: Intestella ESRC-epigenetics funded grant, specifically Prof Caroline Relton, Prof Chris Power, and Dr Matt Suderman. Collaborative projects so far focus on early life adversity and epigenetics. Collaborative projects so far led by our group focus on ageing and functional capacity.
Collaborator Contribution A bi-lateral agreement to collaborate on 1958BC cohort epigenetic data analysis with researchers leading the E4: Intestella ESRC-epigenetics funded grant, specifically Prof Caroline Relton, Prof Chris Power, and Dr Matt Suderman. Collaborative projects so far led by the Bristol group focus on early life adversity and epigenetics.
Impact We performed separate epigenetic profiling in two 1958BC samples of altogether 516 individuals with investigators from the University of Bristol. As a result of our collaboration we have shared our datasets and are now explore research questions in the joint sample of 516 individuals. Research projects focus on ageing and early life adversity.
Start Year 2016
 
Description Additional epigenetic studies in BCS70 in collaboration with UCL 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Further collaborative work between Dr Bell at KCL and Prof Goodman at UCL has resulted in securing additional funding (to Prof Goodman) to carry out epigenetic profiling in additional samples from the BCS70. This has now been approved and work is underway to proceed with epigenetic profiling. The long-term aim would be to profile longitudinal epigenomics in a sample of individuals form the BCS70 to study the role of different exposures on the epigenome and with respect to ageing outcomes.
Collaborator Contribution Prof Goodman, in collaboration with Dr Bell and Dr Ploubidis secured funding to perform epigenetic profiling in additional samples, including samples from BCS70. Work is underway to proceed with sample selection and epigenetic profiling, which will be performed in collaboration with Dr Bell.
Impact No outputs yet.
Start Year 2019
 
Description "Age and cohort-related DNA methylome variation captures generational effects in UK population-cohorts", the First Advances in Precision Medicine conference, Doha, QATAR, November 2021 (delivered online). 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at a scientific conference on ageing
Year(s) Of Engagement Activity 2021
 
Description "Epigenetics, fertility, and health: insights from twin studies", 3rd Annual CeFH Symposium, Oslo, Sept 2020 (delivered online). 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact This was the 3rd Research Symposium of the Centre for Fertility and Health at the Norwegian Institute of Public Health, Oslo, Norway. The Symposium aims to advance the understanding of how changes in patterns of fertility and family structure influence child and adult health through social and biological pathways, using cross-discipline collaboration. The Symposium gave an overview and discussion of methodological approaches applied in economics, sociology, epidemiology and genetics to study family and health.

There were over 10 presentations from international researchers presenting recent findings in the field of family, fertility and health to an audience of international researchers, graduate students, industry members.
Year(s) Of Engagement Activity 2020
 
Description "Genetic impacts on human methylome variation", CANSSI Ontario STAGE program International Speaker Seminar Series, Toronto, Canada, November 2021 (delivered online). 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at an international seminar series host by University of Toronto
Year(s) Of Engagement Activity 2021
 
Description "Genetic impacts on human methylome variation", Epigenetic Inheritance Symposium, ETH Zurich, Switzerland, August 2021 (delivered online). 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at a symposium on epigenetics
Year(s) Of Engagement Activity 2021
 
Description "Genetic impacts on human methylome variation", FASEB conference "The Epigenome in Human Health and Diseases", University of Lorraine, October 2021 (delivered online). 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at an international conference
Year(s) Of Engagement Activity 2021
 
Description Age and cohort-related DNA methylome variation captures generational effects in UK population-cohorts 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at an international conference, the First Advances in Precision Medicine conference, Doha, QATAR, November 2021.
Year(s) Of Engagement Activity 2021
 
Description ESSN network grant webpage 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Website to disseminate the research within the context of the Epigenetics in the Social Sciences Network.
Year(s) Of Engagement Activity 2015,2016,2017
URL http://www.bristol.ac.uk/integrative-epidemiology/epigenetics-social-science-network/research-projec...
 
Description Epigenetics in twins: drivers and consequences 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at the International Society for Twin Studies, Twin Congress 2023, Budapest, Hungary, June 2023
Year(s) Of Engagement Activity 2023
 
Description Epigenomics of common diseases conference (JCF 2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Juan E. Castillo-Fernandez and Jordana T. Bell. Enrichment of local genetic impacts on DNA methylation at enhancers and insulators. The 7th Epigenomics of Common Diseases conference, Hinxton, UK, 14-17 Nov 2017

This oral presentation identifies associations between genetic variation and DNA methylation levels, with strong effects at enhancers and insulators. Current work is extending these analyses to other UK cohorts including NCDS and NSHD.
Year(s) Of Engagement Activity 2017
 
Description Genetic and environmental impacts on the human methylome: towards improvement of cardio-metabolic health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited talk at the Department of Molecular and Medical Genetics, King's College London, November 2023.
Year(s) Of Engagement Activity 2023
 
Description Genetic impacts on DNA methylation levels in the context of DOHAD 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at the international DOHAD congress, Vancouver, August 2022.
Year(s) Of Engagement Activity 2022
 
Description High-dimensional integrative data analysis for personalized medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited talk at the Karolinska Institute, Stockholm, Sweden, October 2023. (delivered online)
Year(s) Of Engagement Activity 2023
 
Description Organised the Epigenetics and Social Science Network Meeting in London 2017 and gave a talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact We organised an Epigenetics and Social Science Network meeting in London on 20 June 2017 to share progress and make plans for the future. All eight projects in the network presented their work and results so far, including us. In addition, we heard from Professor Chris Power who highlighted other projects sponsored by ESRC and BBSRC, in particular 'Reversibility network on later life interventions to reverse effects of early life adversity'. There was discussion about how the network can work jointly on hosting and orgasing future events.
Year(s) Of Engagement Activity 2017
URL http://www.bristol.ac.uk/integrative-epidemiology/epigenetics-social-science-network/news/2017/epige...
 
Description Talk at 2nd Tore Nilson/Karolinska Institutet conference on clinical epigenetics in Sweden (2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference talk title: 'Twin Epigenomics', The 2nd Tore Nilson/Karolinska Institutet conference on clinical epigenetics, Stockholm, Sweden, April 2017.

Jordana Bell delivered an invited talk on twin studies and their value in studying the epigenome to an audience of epigeneticists, including a number of international world-leaders in epigenetics. Dr Bell discussed ongoing research projects and potential opportunities for future collaborative projects.
Year(s) Of Engagement Activity 2017
 
Description Talk at Genomic Informatics Conference (2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We (JTB) presented our work at the Genomic Informatics 2018 conferece (Wellcome Genome Campus; Sept 2018) on the topic of "Interpreting human methylome variation: genetic impacts on variation"
Year(s) Of Engagement Activity 2018
 
Description Talk at the 26th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI) (2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We (JTB) were invited to present our results at the 26th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI; London, Nov 2018) on the topic of "Epigenetics and ART".
Year(s) Of Engagement Activity 2018
 
Description Talk at the 4th Canadian Conference on Epigenetics (2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference talk title: 'Epigenetics in twins', The 4th Canadian Conference on Epigenetics, Whistler, BC, Canada, Nov 2017.


Jordana Bell delivered an invited talk on twin studies and their value in studying the epigenome. Dr Bell discussed ongoing research projects and potential opportunities for future collaborative projects. This gave her an opportunity to meet existing collaborators as well as extend her research network.
Year(s) Of Engagement Activity 2017
 
Description Talk at the 6th Building Bridges Symposium in Finland (2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference talk title: 'Epigenetic studies in twins', The 6th Building Bridges Symposium: Epigenetics in Clinical and Translational Research, Helsinki, Finland, Oct 2017.

Jordana Bell delivered an invited talk on twin studies and their value in studying the epigenome to an audience of epigeneticists or researchers who were interested in working in epigenetics - primarily from Finland, but also including several international world-leaders in epigenetics. Dr Bell discussed ongoing research projects and potential opportunities for future collaborative projects.
Year(s) Of Engagement Activity 2017
 
Description Talk at the Computational Epigenomics Workshop at the 17th European Conference on Computational Biology (JCF 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We (JC-F) presented our results at the Computational Epigenomics workshop at the 17th European Conference on Computational Biology (Athens, Sept 2018) on the topic of "Identification of DNA methylation changes associated to ageing outcomes in human population samples".
Year(s) Of Engagement Activity 2018
 
Description Talk at the EMBL-EBI Industry Programme Workshop on Epigenetics for ageing and disease (2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact We (JTB) were invited to present our findings at the EMBL-EBI Industry Programme Workshop on Epigenetics for ageing and disease (EBI, Wellcome Genome Campus, Oct 2018) on the topic of "Ageing signatures in the DNA methylome across UK cohorts"
Year(s) Of Engagement Activity 2018
 
Description Talk at the ESRC/BBSRC Epigenetics Showcase event in London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Supporters
Results and Impact An epigenetics showcase event to a mixed audience predominantly of academics and representatives from funding bodies, with some policy makers; approximately 60 audience members.
Year(s) Of Engagement Activity 2019
 
Description Talk at the Epigenetics and Social Science Network Meeting in Durham (2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact We attended and presented our research at the Epigenetics and Social Science Network meeting in Durham in March 2018 to share progress and make plans for the future of the network. All eight projects in the network presented their work and results so far. In addition, we heard from Professor Meena Kumari and representatives from the research councils.
Year(s) Of Engagement Activity 2018
 
Description Talk at the Epigenetics and Social Science Network Meeting in Durham (JCF 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact We (JC-F) presented our results at the Epigenetics and Social Science Network meeting in Durham in March 2018 and discussed plans for future work and the future of the network. The audience consisted of academics involved in related research and representatives from the research councils.
Year(s) Of Engagement Activity 2018
 
Description Talk at the Epigenetics and Social Science Network meeting in Durham (JM 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact We (JM) presented our results at the Epigenetics and Social Science Network meeting in Durham in March 2018 and discussed plans for future work and the future of the network. The audience consisted of academics involved in related research and representatives from the research councils.
Year(s) Of Engagement Activity 2018
 
Description Talk at the Longitudinal Studies Wellcome Conference (RH 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We (RH) presented our results at Longitudinal Studies Wellcome Conference (Wellcome Genome Campus; 30 May-1st June 2018) on the topic of "Epigenetic age and functional markers of health span".
Year(s) Of Engagement Activity 2018
 
Description Talk at the NCDS at 60 scientific conference (2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference talk title: 'Cross-sectional and longitudinal changes in DNA methylation with age across four UK population based cohorts', The National Child Development Study (NCDS) 60 years of our lives conference, London, UK, March 2018.

Jordana Bell delivered an invited talk in the session "Frontiers in biological research" to a broad audience, which included economists, social scientists, experts in cohort studies, and child developmental psychologists. Dr Bell discussed potential opportunities for future collaborative projects and extended her research network.
Year(s) Of Engagement Activity 2018
 
Description Talk at the Wellcome Trust Mathematical Genomics and Medicine PhD programme at the University of Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited research seminar to the mathematical genomics PhD students at the University of Cambridge - audience consisted of ~50 predominantly PhD students, postdocs, and academics.
Year(s) Of Engagement Activity 2019
 
Description Talk at the Wellcome Trust Mathematical Genomics and Medicine PhD programme at the University of Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Invited research seminar to the mathematical genomics PhD students at the University of Cambridge - audience consisted of ~50 predominantly PhD students, postdocs, and academics.
Year(s) Of Engagement Activity 2021