Imprinting methylation; early life influences and later cognition and mood.

Lead Research Organisation: University of Aberdeen
Department Name: Sch of Medicine, Medical Sci & Nutrition

Abstract

There is much evidence that early life experiences (from fetal life through childhood) can influence adult outcomes. However, the pathways and mechanisms by which earlier experiences become embedded in an individual's life-course and how they influence health and behavioral outcomes are still not clear. Epigenetics provides a key emerging platform for interdisciplinary research among the biological and social sciences to further understand the complex interactions between social phenomena and human biology and behavior. Epigenetics refers to information in the human genome other than that in the DNA sequence. Imprinting refers to a special kind of epigenetic marking of genes that occurs very early in development and is then often stable across the life course. There is increasing evidence for the importance of these epigenetic factors in brain function, cognition, mood and behavior.

We aim to investigate the effect of the early social environment on epigenetic status and its relationship to cognition and mood in later life. The proposed study exploits existing data and samples collected from two important UK longitudinal studies (Aberdeen Birth Cohorts born in 1921 and 1936). The data held includes extensive information on early social environment, later life exposures, and changes in cognition, mood, and brain volumes into old age. We believe that our hypotheses, relating to germline imprints, is particularly appropriate to such longitudinal study designs. These epigenetic marks are influenced by the early environment, they are stable over decades, they typically occur in multiple tissue types, and they are known to influence behavior.

This is a truly multidisciplinary project involving collaboration between researchers in three UK centers (University of Aberdeen, University College London, and University of Cambridge) with strong track records in the areas relevant to the call. It involves a number of social scientists and biological scientists and crucially involves the training of a post-doctoral scientist to work beyond traditional boundaries and contribute to the development of a new discipline that spans the biological and social sciences.

This work is naturally complemented by our existing programme of research on the effects of the early environment on imprinting methylation in a contemporary birth cohort where we have extensive information on maternal diet, nutritional and socioeconomic status, maternal health, birth outcome, etc. In that study we are currently measuring in newborn blood the same imprinted regions that will be studied here. That work will be used to inform the interpretation of the early life findings from the proposed study and identify contemporary early exposures that influence imprints linked to later cognition and mood.

We believe that this research provides a unique opportunity to; 1) directly measure the strength of association between early life factors, imprinting and cognition; 2) produce knowledge to underpin the development of evidence based strategies at different life stages to improve mental health and wellbeing; 3) generate specific hypotheses that can be tested in future studies in other human cohorts and brain tissue, such as that available within the MRC brain bank, 4) produce knowledge to inform the development of work in other species and model systems, and 5) contribute to the development of a new research discipline that encompasses the molecular and social sciences.

Planned Impact

Our research will contribute fundamental new knowledge with a range of potential beneficiaries in the public sector, academia, and the general public (including the participants in this study). This project has the potential to impact on; 1) the wellbeing of individuals, and society as a whole, 2) healthcare providers such as the NHS, 3) policy makers, 4) social services, 5) the commercial sector and 6) clinical and basic scientists and the wider academic community.

This research will; 1) produce knowledge to underpin the development of evidence based strategies at different life stages to improve mental health and wellbeing; 2) generate specific hypotheses that can be tested in future studies in other human cohorts and brain tissue, such as that available within the MRC brain bank, and 3) produce knowledge to inform the development of work in other species and model systems.

This work exploits existing resources to "study alternative pathways to explain the underlying factors of the diverse human responses to environmental signals." It seeks to "uncover pathways and mechanisms for modifying or reversing lasting legacies of adversity, and identifying biomarkers of exposure to adverse early experiences".

Cognition and mood are linked to early mortality and morbidity (e.g. cardiovascular disease, stroke, and respiratory disease). Cognitive decline and dementias are putting an increasing strain on healthcare budgets in our increasingly aging society. Understanding the factors early in life that influence cognition and mood, the mechanism through which they may do this, and the factors in later life that may modulate these effects, would assist in the development of effective strategies to improve social welfare and public services and health and well-being. Such improvements would be of considerable economic value and would help reduce the pressure on health services. The identification of epigenetic markers of cognition and mood in later life would also be useful in the development of better screening methods and the early identification of 'at risk' groups for targeted interventions. Elucidation of the importance of life-stage and identification of the factors which influence cognition across the life-course will help the public sector and policy makers, in the UK and internationally, develop evidence based strategies to improve lifelong cognitive health and its associated outcomes.

Elucidation of epigenetic markers related to cognition and mood has the potential to point to new areas of research and specific drug targets to improve cognition and cognitive outcomes. This could result in the development of new technologies to benefit human health, social welfare and public services in addition to providing commercial opportunities.

The research proposed here will also be relevant to academics in many of the life sciences including; human behavior and psychology, basic biology and the study of genome regulation and function. This project brings together the "biological and social sciences to further understand the complex interactions between social phenomena and human biology and behaviour." It has the potential to contribute to the development of a new research discipline that encompasses the molecular and social sciences.

Publications

10 25 50
 
Description The period of the award has been extended and it is still active but the laboratory analysis is complete and the key objectives for this stage in the project have been met. One manuscript has been published and we are in the process of writing up the rest of the results for publication.
Exploitation Route This will be realised at later stages in the project through the work set out in our Pathways to Impact.
Sectors Communities and Social Services/Policy,Creative Economy,Education,Healthcare,Pharmaceuticals and Medical Biotechnology

URL https://app.researchfish.com/getform/0/dissemination-to-non-academic-audiences?action=add&zone=portfolio&destination=awards/dissemination-to-non-academic-audiences/0%3Fgorderby%3Dorganisation%26ob%3Dcreated%26ds%3D0%26ne%3D%26zone%3Dportfolio%26filter%3DESRC-ES/N00048X/1%26orderby%3Dcreated%26offset%3D0&filter=ESRC-ES/N00048X/1
 
Description The project is still at an early stage but we have begun to disseminate information and the concepts underpinning this novel area linking biology to the social sciences. We have promoted understanding of this emerging area to the general public at a reunion event for the two study cohorts involved in this work. We have also highlighted the implications of our research for government policy in relation to the transgenerational transmission of disadvantage in apresentation to the Child and Maternal Health Division of Scottish Government. The project is due to be completed in the next few months. As the data are published we will translate the findings into lay summaries and publicise as set out in the study Pathways to Impact.
First Year Of Impact 2019
Impact Types Policy & public services

 
Description A briefing on epigenetics and the implications of our research for government policy in relation to the transgenerational transmission of disadvantage was presented to the Child and Maternal Health Division of Scottish Government and related areas (e.g. obesity).
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description A Pilot Study of Epigenetic Imprinting and Breast Cancer using Next Generation Sequencing
Amount £9,399 (GBP)
Organisation Friends of ANCHOR 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2015 
End 06/2016
 
Description A Pilot Study of the Role of Carnitine Palmitoyltransferase-1 in the Progression of Breast Cancer
Amount £9,763 (GBP)
Organisation Pathological Society of Great Britain & Ireland 
Sector Learned Society
Country United Kingdom
Start 04/2017 
End 03/2018
 
Description Breast Cancer Epigenetics
Amount £14,350 (GBP)
Funding ID RG13415 
Organisation University of Aberdeen 
Department Development Trust
Sector Charity/Non Profit
Country United Kingdom
Start 02/2016 
End 02/2017
 
Description Environmental Metabolic and Molecular Causes of Breast Cancer
Amount £9,350 (GBP)
Organisation University of Aberdeen 
Department Development Trust
Sector Charity/Non Profit
Country United Kingdom
Start 07/2017 
End 07/2018
 
Description GCRF Action against Stunting Hub
Amount £19,760,000 (GBP)
Funding ID MR/S01313X/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2019 
End 02/2024
 
Description Unlocking the Joint Morphogenic Code in Mesenchymal Stem Cells from Human Synovium
Amount £327,874 (GBP)
Funding ID 21800 
Organisation Versus Arthritis 
Start 06/2018 
End 05/2021
 
Title development of NGS bisulphite sequencing of targeted imprints 
Description NGS bisulphite sequencing of targeted imprints. The assay designs and protocols will be included in publications submitted this year. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? No  
Impact The immediate impact is that development of these assays has allowed us to carry out our planned analysis within this project. The wider impact to others will come on publication of the methods. 
 
Title Adding epigenetic data to Aberdeen Birth Cohort database 
Description Addition of epigenetic data to cognitive and phenotypic database. Results will be made publicly available on completion of the project and publication of all findings. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Allows research team to complete statistical analysis and modelling. 
 
Title Public availability of research data 
Description The paper below reporting findings from this study has been published and the study data has been made available to researchers in accordance with the policy of PLoS One. Lorgen-Ritchie, M., A. D. Murray, A. C. Ferguson-Smith, M. Richards, G. W. Horgan, L. H. Phillips, G. Hoad, I. Gall, K. Harrison, G. McNeill, M. Ito, and P. Haggarty. 2019. 'Imprinting methylation in SNRPN and MEST1 in adult blood predicts cognitive ability', PLoS One, 14: e0211799. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact The publication is the major output so far but this was only published in the last month. We expect to see impacts when researchers begin to use the data we have made available. 
URL https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0211799&type=printable
 
Description Global Challenges Research Fund International Collaboration using Epigenetics 
Organisation Digital Green
Country India 
Sector Private 
PI Contribution Member of a of a BBSRC led delegation to Nepal to develop UK-international collaboration in the area of nutrition and health. Our specific contribution was in the area of epigenetics and nutrition part of which was based on the methods and findings from this ESRC funded study. The discussions resulted in the preparation of a submission ("GCRF Action Against Stunting Hub") under the GCRF-Hub call. The hub was funded in 2019 and work has begun.
Collaborator Contribution This is a multi-disciplinary project in LMICs with each partner making a unique contribution. UK Collaborators: London Sch of Hygiene and Trop Medicine, MRC Unit, The Gambia, Liverpool School of Tropical, Int Livestock Research Institute Medicine, Royal Veterinary College, School of Oriental & African Studies, University College London, University of Brighton International collaborators: University of Indonesia, National Institute of Nutrition, India. Université Cheikh Anta DIOP, Dakar, Senegal. Digital Green.
Impact Full funding for the GCRF Action Against Stunting Hub (MR/S01313X/1).
Start Year 2019
 
Description Global Challenges Research Fund International Collaboration using Epigenetics 
Organisation International Livestock Research Institute (ILRI)
Country Kenya 
Sector Charity/Non Profit 
PI Contribution Member of a of a BBSRC led delegation to Nepal to develop UK-international collaboration in the area of nutrition and health. Our specific contribution was in the area of epigenetics and nutrition part of which was based on the methods and findings from this ESRC funded study. The discussions resulted in the preparation of a submission ("GCRF Action Against Stunting Hub") under the GCRF-Hub call. The hub was funded in 2019 and work has begun.
Collaborator Contribution This is a multi-disciplinary project in LMICs with each partner making a unique contribution. UK Collaborators: London Sch of Hygiene and Trop Medicine, MRC Unit, The Gambia, Liverpool School of Tropical, Int Livestock Research Institute Medicine, Royal Veterinary College, School of Oriental & African Studies, University College London, University of Brighton International collaborators: University of Indonesia, National Institute of Nutrition, India. Université Cheikh Anta DIOP, Dakar, Senegal. Digital Green.
Impact Full funding for the GCRF Action Against Stunting Hub (MR/S01313X/1).
Start Year 2019
 
Description Global Challenges Research Fund International Collaboration using Epigenetics 
Organisation Liverpool School of Tropical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Member of a of a BBSRC led delegation to Nepal to develop UK-international collaboration in the area of nutrition and health. Our specific contribution was in the area of epigenetics and nutrition part of which was based on the methods and findings from this ESRC funded study. The discussions resulted in the preparation of a submission ("GCRF Action Against Stunting Hub") under the GCRF-Hub call. The hub was funded in 2019 and work has begun.
Collaborator Contribution This is a multi-disciplinary project in LMICs with each partner making a unique contribution. UK Collaborators: London Sch of Hygiene and Trop Medicine, MRC Unit, The Gambia, Liverpool School of Tropical, Int Livestock Research Institute Medicine, Royal Veterinary College, School of Oriental & African Studies, University College London, University of Brighton International collaborators: University of Indonesia, National Institute of Nutrition, India. Université Cheikh Anta DIOP, Dakar, Senegal. Digital Green.
Impact Full funding for the GCRF Action Against Stunting Hub (MR/S01313X/1).
Start Year 2019
 
Description Global Challenges Research Fund International Collaboration using Epigenetics 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution Member of a of a BBSRC led delegation to Nepal to develop UK-international collaboration in the area of nutrition and health. Our specific contribution was in the area of epigenetics and nutrition part of which was based on the methods and findings from this ESRC funded study. The discussions resulted in the preparation of a submission ("GCRF Action Against Stunting Hub") under the GCRF-Hub call. The hub was funded in 2019 and work has begun.
Collaborator Contribution This is a multi-disciplinary project in LMICs with each partner making a unique contribution. UK Collaborators: London Sch of Hygiene and Trop Medicine, MRC Unit, The Gambia, Liverpool School of Tropical, Int Livestock Research Institute Medicine, Royal Veterinary College, School of Oriental & African Studies, University College London, University of Brighton International collaborators: University of Indonesia, National Institute of Nutrition, India. Université Cheikh Anta DIOP, Dakar, Senegal. Digital Green.
Impact Full funding for the GCRF Action Against Stunting Hub (MR/S01313X/1).
Start Year 2019
 
Description Global Challenges Research Fund International Collaboration using Epigenetics 
Organisation Royal Veterinary College (RVC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Member of a of a BBSRC led delegation to Nepal to develop UK-international collaboration in the area of nutrition and health. Our specific contribution was in the area of epigenetics and nutrition part of which was based on the methods and findings from this ESRC funded study. The discussions resulted in the preparation of a submission ("GCRF Action Against Stunting Hub") under the GCRF-Hub call. The hub was funded in 2019 and work has begun.
Collaborator Contribution This is a multi-disciplinary project in LMICs with each partner making a unique contribution. UK Collaborators: London Sch of Hygiene and Trop Medicine, MRC Unit, The Gambia, Liverpool School of Tropical, Int Livestock Research Institute Medicine, Royal Veterinary College, School of Oriental & African Studies, University College London, University of Brighton International collaborators: University of Indonesia, National Institute of Nutrition, India. Université Cheikh Anta DIOP, Dakar, Senegal. Digital Green.
Impact Full funding for the GCRF Action Against Stunting Hub (MR/S01313X/1).
Start Year 2019
 
Description Global Challenges Research Fund International Collaboration using Epigenetics 
Organisation School of Oriental and African Studies (University of London)
Country United Kingdom 
Sector Academic/University 
PI Contribution Member of a of a BBSRC led delegation to Nepal to develop UK-international collaboration in the area of nutrition and health. Our specific contribution was in the area of epigenetics and nutrition part of which was based on the methods and findings from this ESRC funded study. The discussions resulted in the preparation of a submission ("GCRF Action Against Stunting Hub") under the GCRF-Hub call. The hub was funded in 2019 and work has begun.
Collaborator Contribution This is a multi-disciplinary project in LMICs with each partner making a unique contribution. UK Collaborators: London Sch of Hygiene and Trop Medicine, MRC Unit, The Gambia, Liverpool School of Tropical, Int Livestock Research Institute Medicine, Royal Veterinary College, School of Oriental & African Studies, University College London, University of Brighton International collaborators: University of Indonesia, National Institute of Nutrition, India. Université Cheikh Anta DIOP, Dakar, Senegal. Digital Green.
Impact Full funding for the GCRF Action Against Stunting Hub (MR/S01313X/1).
Start Year 2019
 
Description Global Challenges Research Fund International Collaboration using Epigenetics 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Member of a of a BBSRC led delegation to Nepal to develop UK-international collaboration in the area of nutrition and health. Our specific contribution was in the area of epigenetics and nutrition part of which was based on the methods and findings from this ESRC funded study. The discussions resulted in the preparation of a submission ("GCRF Action Against Stunting Hub") under the GCRF-Hub call. The hub was funded in 2019 and work has begun.
Collaborator Contribution This is a multi-disciplinary project in LMICs with each partner making a unique contribution. UK Collaborators: London Sch of Hygiene and Trop Medicine, MRC Unit, The Gambia, Liverpool School of Tropical, Int Livestock Research Institute Medicine, Royal Veterinary College, School of Oriental & African Studies, University College London, University of Brighton International collaborators: University of Indonesia, National Institute of Nutrition, India. Université Cheikh Anta DIOP, Dakar, Senegal. Digital Green.
Impact Full funding for the GCRF Action Against Stunting Hub (MR/S01313X/1).
Start Year 2019
 
Description Global Challenges Research Fund International Collaboration using Epigenetics 
Organisation University of Indonesia
Country Indonesia 
Sector Academic/University 
PI Contribution Member of a of a BBSRC led delegation to Nepal to develop UK-international collaboration in the area of nutrition and health. Our specific contribution was in the area of epigenetics and nutrition part of which was based on the methods and findings from this ESRC funded study. The discussions resulted in the preparation of a submission ("GCRF Action Against Stunting Hub") under the GCRF-Hub call. The hub was funded in 2019 and work has begun.
Collaborator Contribution This is a multi-disciplinary project in LMICs with each partner making a unique contribution. UK Collaborators: London Sch of Hygiene and Trop Medicine, MRC Unit, The Gambia, Liverpool School of Tropical, Int Livestock Research Institute Medicine, Royal Veterinary College, School of Oriental & African Studies, University College London, University of Brighton International collaborators: University of Indonesia, National Institute of Nutrition, India. Université Cheikh Anta DIOP, Dakar, Senegal. Digital Green.
Impact Full funding for the GCRF Action Against Stunting Hub (MR/S01313X/1).
Start Year 2019
 
Description ESRC Festival of Social Science 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Presentation on study aims and scientific and societal objectives as part of the ESRC Festival of Social Science (Aberdeen event) which was open to the public and was well attended.
Year(s) Of Engagement Activity 2018
 
Description Aberdeen Birth Cohort of 1936 reunion event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Study participants or study members
Results and Impact A reunion event was held in August 2016 for members of the Aberdeen Birth Cohort of 1936 (ABC36). During the event, cohort members and their families were updated on recent results arising from the cohort data and of ongoing studies, including our current study using Next Generation Bisulphite Sequencing to extensively quantify methylation profiles in imprinted genes in DNA obtained from ABC participants (funded by grant ES/N00048X/I). The cohort members showed a keen interest when researchers got the chance to mingle and discuss studies over tea, coffee and cakes, and the researchers were rewarded with lively stories and fond memories from the past.
Year(s) Of Engagement Activity 2016
 
Description ESRC and BBSRC Epigenetics and Social Science Network inaugural meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The inaugural meeting of the ESRC/BBSRC biosocial epigenetics initiative was held in Bristol and attended by the groups participating in the programme. The aim of this meeting was to encourage cross-disciplinary collaboration and to promote a wider understanding of the programme and individual projects funded under this initiative. The aims and objectives of this project were presented to the wider research network.
Year(s) Of Engagement Activity 2015
URL https://app.researchfish.com/getform/0/dissemination-to-non-academic-audiences?action=add&zone=portf...
 
Description Presentation at Aberdeen MayFest Public open doors event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Raising awareness of Biosocial research and its practical value.
Year(s) Of Engagement Activity 2018