NutriPROGRAM: Early-life Nutritional Programming of Metabolic Health through Epigenetic Pathways
Lead Research Organisation:
University of Bristol
Department Name: Oral and Dental Science
Abstract
Pregnancy and infancy are critical periods for nutritional programming of metabolic health. Epigenetic changes seem to have a crucial role in pathways leading from early-life nutrition to metabolic health across the life course. NutriPROGRAM will study key maternal and infant nutrition-related exposures in relation to DNA methylation in mothers and offspring at different ages, and metabolic health across the life course. NutriPROGRAM will specifically focus on cause-and-effect relationships, reversibility of DNA methylation changes by nutrition, lifestyle, physical activity and microbiota, functional consequences of DNA methylation changes and translation into preventive or population-health strategies. Eventually, NutriPROGRAM will develop a sustainable, translational, international collaboration for studies on nutrition and epigenetics and their role in sustaining good health throughout the life course.
Technical Summary
Pregnancy and infancy are critical periods for nutritional programming of metabolic health. Epigenetic changes seem to have a crucial role in pathways leading from early-life nutrition to metabolic health across the life course. NutriPROGRAM will study key maternal and infant nutrition-related exposures in relation to DNA methylation in mothers and offspring at different ages, and metabolic health outcomes across the life course. It will involve: (1) integrating sets of early-life nutritional factors in mothers and infants; (2) observational and intervention studies across the life course on metabolic outcomes including longitudinal growth and fat development, advanced imaging for body fat, metabolomic profiles and clinical outcomes; (3) cause-and-effect relationships of DNA methylation in the associations of nutrition-related factors and metabolic outcomes across the life course, by advanced causal inference approaches; (4) modification of DNA methylation changes by nutrition, lifestyle, physical activity and microbiota; (5) functional consequences of differences in DNA methylation using RNA expression and tissue specific approaches; and (6) translation into preventive or population-health strategies. NutriPROGRAM will capitalize on rich, existing and complementary nutritional, metabolic and epigenetic datasets from observational and intervention studies in pregnancy, childhood and adulthood, together covering the full life course. It will use knowledge and data infrastructures from different collaborative consortia including the Horizon2020 DynaHEALTH and LifeCycle Projects, the ERA-HDHL ALPHABET project, and the Pregnancy and Childhood Epigenetics (PACE) Consortium. Eventually, NutriPROGRAM will develop a sustainable, translational, international collaboration for current and future studies on nutrition and epigenetics and their role in sustaining good health throughout the lifecourse.
Planned Impact
NutriPROGRAM will create a set of harmonised and integrated nutrition-related exposure indices that can serve as important novel and improved tools for scientists studying the relationships between nutrition and health both within and outside of NutriPROGRAM.
NutriPROGRAM will lead to the identification of novel DNA methylation loci with functional roles in the pathways underlying the relation of early-life nutrition and metabolic health, improving the knowledge base for future research and development activities.
NutriPROGRAM will lead to a better understanding of causality and modification of DNA methylation in the pathways leading from early-life nutrition to metabolic health. This will be a starting point for evidence-based preventive strategies and new nutrition-related interventions to reduce the worldwide health-related, economic and societal burden of obesity, dyslipidemia and type 2 diabetes in future generations.
NutriPROGRAM will develop a method for prioritisation of DNA methylation markers for functional follow-up that will be broadly applicable for the wider research community involved in DNA methylation research.
NutriPROGRAM will form a sustainable, translational international network on early-life nutrition, epigenetics and long term metabolic outcomes that will lay the foundation of further research in this area for many years to come.
Effective exploitation and dissemination of research results is an important aspect of the work performed in NutriPROGRAM and will be a focus of attention from the beginning of this project onwards. WP6 will be responsible for the management of dissemination and exploitation. Partners in the consortium will be encouraged to participate in active dissemination strategies, which will include:
- Publishing scientific articles: NutriPROGRAM will produce scientific manuscripts which will be submitted for publication in peer-reviewed journals.
- Presenting work at national and international scientific conferences: Consortium members will present the work performed in the consortium at relevant scientific conferences and will engage in discussions with fellow scientists and other interested conference participants.
- Training activities: Consortium partners will be actively involved in the training of early career researchers, transferring knowledge and skills to contribute to building a strong foundation for their research careers. In addition, all consortium partners are involved in teaching activities in their own and other institutions. These include lectures, seminars and workshops. Relevant results from the work performed in the consortium will be incorporated in these teaching activities.
- Communicating with the general public: NutriPROGRAM will disseminate scientifically credible findings, with appropriate interpretations and explanations, to the general public. Various ways of communication may be used, including traditional media, (institutional) websites and social media.
- Communicating with stakeholders: NutriPROGRAM will effectively translate relevant scientific findings to various stakeholders, including policy makers, healthcare professionals such as obstetricians, midwives, paediatricians and general practitioners, industry and patient organisations.
NutriPROGRAM will lead to the identification of novel DNA methylation loci with functional roles in the pathways underlying the relation of early-life nutrition and metabolic health, improving the knowledge base for future research and development activities.
NutriPROGRAM will lead to a better understanding of causality and modification of DNA methylation in the pathways leading from early-life nutrition to metabolic health. This will be a starting point for evidence-based preventive strategies and new nutrition-related interventions to reduce the worldwide health-related, economic and societal burden of obesity, dyslipidemia and type 2 diabetes in future generations.
NutriPROGRAM will develop a method for prioritisation of DNA methylation markers for functional follow-up that will be broadly applicable for the wider research community involved in DNA methylation research.
NutriPROGRAM will form a sustainable, translational international network on early-life nutrition, epigenetics and long term metabolic outcomes that will lay the foundation of further research in this area for many years to come.
Effective exploitation and dissemination of research results is an important aspect of the work performed in NutriPROGRAM and will be a focus of attention from the beginning of this project onwards. WP6 will be responsible for the management of dissemination and exploitation. Partners in the consortium will be encouraged to participate in active dissemination strategies, which will include:
- Publishing scientific articles: NutriPROGRAM will produce scientific manuscripts which will be submitted for publication in peer-reviewed journals.
- Presenting work at national and international scientific conferences: Consortium members will present the work performed in the consortium at relevant scientific conferences and will engage in discussions with fellow scientists and other interested conference participants.
- Training activities: Consortium partners will be actively involved in the training of early career researchers, transferring knowledge and skills to contribute to building a strong foundation for their research careers. In addition, all consortium partners are involved in teaching activities in their own and other institutions. These include lectures, seminars and workshops. Relevant results from the work performed in the consortium will be incorporated in these teaching activities.
- Communicating with the general public: NutriPROGRAM will disseminate scientifically credible findings, with appropriate interpretations and explanations, to the general public. Various ways of communication may be used, including traditional media, (institutional) websites and social media.
- Communicating with stakeholders: NutriPROGRAM will effectively translate relevant scientific findings to various stakeholders, including policy makers, healthcare professionals such as obstetricians, midwives, paediatricians and general practitioners, industry and patient organisations.
Organisations
- University of Bristol (Lead Research Organisation)
- Biotechnology and Biological Sciences Research Council (Co-funder)
- Barcelona Institute for Global Health (Collaboration)
- University of Bath (Collaboration)
- Cardiff University (Collaboration)
- Erasmus MC (Collaboration)
- GW4 (Collaboration)
- Ludwig Maximilian University of Munich (LMU Munich) (Collaboration)
- Wageningen University & Research (Collaboration)
- UNIVERSITY OF BRITISH COLUMBIA (Collaboration)
- National Institute of Environmental Health Sciences (Collaboration)
- UNIVERSITY OF EXETER (Collaboration)
Publications
Battram T
(2022)
The EWAS Catalog: a database of epigenome-wide association studies.
in Wellcome open research
Battram T
(2022)
The EWAS Catalog: a database of epigenome-wide association studies
in Wellcome Open Research
Caramaschi D
(2022)
Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills.
in Molecular psychiatry
Easey KE
(2021)
The impact of paternal alcohol, tobacco, caffeine use and physical activity on offspring mental health: a systematic review and meta-analysis.
in Reproductive health
Juvinao-Quintero DL
(2021)
DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts.
in Clinical epigenetics
Juvinao-Quintero DL
(2019)
DNA Methylation and Type 2 Diabetes: the Use of Mendelian Randomization to Assess Causality.
in Current genetic medicine reports
Description | Co-director of the MSc in Reproduction and Development |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Gemma Sharp is the co-director of the University of Bristol's highly successful MSc in Reproduction and Development. Students include practicing midwifes, junior doctors, researchers and embryologists. The course equips them with the necessary skills to improve their practice and critically appraise, design and conduct relevant research. |
URL | http://www.bristol.ac.uk/medical-school/study/postgraduate/reproduction-development/ |
Description | Epigenetic Epidemiology short course |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | I developed and delivered a one week course on epigenetic epidemiology in 2019 and again in 2020. Participants ranged from masters to professorial level. The course was very well-received and participants reported feeling confident that they had achieved the intended learning outcomes. Several are now conducting their own genetic/epigenetic studies. |
URL | https://www.bristol.ac.uk/medical-school/study/short-courses/epigenetic-epidemiology/ |
Description | Genetic and Epigenetic Epidemiology (EEPE) course |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Gemma Sharp and Rebecca Richmond (along with David Evans and Gib Hemani) co-developed and delivered a one week course on genetic and epigenetic epidemiology in Florence. Participants ranged from masters to professorial level. The course was very well-received and participants reported feeling confident that they had achieved the intended learning outcomes. Several are now conducting their own genetic/epigenetic studies. |
URL | https://eepe.org/courses/ |
Description | Lectures at LSHTM |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Gemma Sharp was invited to give two lectures to masters students at the London School of Hygiene and Tropical Medicine: "Minimising bias and confounding in observational epidemiology" and "Mendelian Randomization". These will take place on March 17th 2020. The lectures are intended to introduce students to these important areas and methods in observational epidemiology and equip them with the skills to critically appraise, design and conduct high quality epidemiological research. |
Description | MSc in Epidemiology - unit lead of 'Molecular Epidemiology for Noncommunicable Disease' |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Gemma Sharp co-developed from scratch and now co-delivers a unit on Molecular Epidemiology as part of the University of Bristol's MSc in Epidemiology. The unit introduces masters students to molecular (genetic and epigenetic) epidemiology and equips them with the skills to critically appraise, design and conduct high quality epidemiological research. |
URL | https://www.bris.ac.uk/unit-programme-catalogue/UnitDetails.jsa;jsessionid=2BBAB6E8979AB5B406936FBF3... |
Description | Workshop on harmonisation of data in multicohort studies |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Gemma Sharp gave a talk as part of a half-day course on data harmonization in observational studies at the DOHaD 2019 world congress in Melbourne. Participants ranged from masters to professorial level. The course was very well-received and participants reported feeling confident that they had achieved the intended learning outcomes. Several are now conducting their own multi cohort studies. |
URL | http://www.cvent.com/events/2019-dohad-international/custom-132-828d23c3caf043c0ae6449de8d7bfbc3.asp... |
Description | Workshop on triangulation |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Gemma Sharp co-developed and delivered a half-day course on triangulation in observational studies at the DOHaD 2019 world congress in Melbourne. Participants ranged from masters to professorial level. The course was very well-received and participants reported feeling confident that they had achieved the intended learning outcomes. Several are now conducting their own triangulation studies. |
URL | http://www.cvent.com/events/2019-dohad-international/custom-132-828d23c3caf043c0ae6449de8d7bfbc3.asp... |
Description | GW4 Development Award |
Amount | £5,000 (GBP) |
Organisation | GW4 |
Sector | Academic/University |
Country | United Kingdom |
Start | 12/2022 |
End | 12/2023 |
Description | GW4 Generator Award |
Amount | £14,800 (GBP) |
Organisation | GW4 |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2021 |
End | 11/2021 |
Description | Improving mental health outcomes in children born with an orofacial cleft: Identifying children at most risk to target clinical provision |
Amount | £608,551 (GBP) |
Funding ID | MR/W020297/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2022 |
End | 08/2025 |
Description | MGLE PhD studentship to Gemma Sawyer: exploration of bidirectional relationships between menstrual and social wellbeing |
Amount | £130,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2021 |
End | 10/2025 |
Description | Wellcome Trust PhD in Molecular, Genetic and Lifecourse Epidemiology - studentship to Florence Martin |
Amount | £130,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2020 |
End | 10/2024 |
Description | Wellcome Trust PhD in Molecular, Genetic and Lifecourse Epidemiology - studentship to Peiyuan Huang |
Amount | £130,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2020 |
End | 10/2024 |
Title | Paternal BMI meta-EWAS results |
Description | This project explores associations between paternal body mass index around the time of conception and offspring DNA methylation in cord blood at birth and peripheral whole blood at childhood. Independent cohorts carried out epigenome-wise association studies (EWAS) according to a pre-specified analysis plan. The summary statistics from these EWAS were then meta-analysed. This dataset provides the full summary statistics for the project. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | A paper describing this study has been published and the data has been uploaded to the EWAS catalog for further use and dissemination by other groups. |
URL | https://dataverse.harvard.edu/dataverse/pace_paternal_bmi_methylation |
Description | 4M consortium |
Organisation | Cardiff University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Gemma Sharp established the Menarche, Menstruation, Menopause and Mental health (4M) consortium using funding from the GW4 Alliance (generator award: £14800). The consortium brings together researchers from different disciplines and institutions, with a shared interest in the intersection of menstrual and mental health. This includes researchers interested in using molecular epidemiological approaches to conduct research in this area. |
Collaborator Contribution | The 4M consortium includes partners from Bath, Cardiff and Exeter University, as well as external stakeholders from charities, patient groups, the NHS, government departments, and the United Nations Population Fund (UNFPA). |
Impact | We have run several workshops, including a three day in-person grant writing retreat. We have developed and submitted four grant applications for further funding. |
Start Year | 2021 |
Description | 4M consortium |
Organisation | GW4 |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Gemma Sharp established the Menarche, Menstruation, Menopause and Mental health (4M) consortium using funding from the GW4 Alliance (generator award: £14800). The consortium brings together researchers from different disciplines and institutions, with a shared interest in the intersection of menstrual and mental health. This includes researchers interested in using molecular epidemiological approaches to conduct research in this area. |
Collaborator Contribution | The 4M consortium includes partners from Bath, Cardiff and Exeter University, as well as external stakeholders from charities, patient groups, the NHS, government departments, and the United Nations Population Fund (UNFPA). |
Impact | We have run several workshops, including a three day in-person grant writing retreat. We have developed and submitted four grant applications for further funding. |
Start Year | 2021 |
Description | 4M consortium |
Organisation | University of Bath |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Gemma Sharp established the Menarche, Menstruation, Menopause and Mental health (4M) consortium using funding from the GW4 Alliance (generator award: £14800). The consortium brings together researchers from different disciplines and institutions, with a shared interest in the intersection of menstrual and mental health. This includes researchers interested in using molecular epidemiological approaches to conduct research in this area. |
Collaborator Contribution | The 4M consortium includes partners from Bath, Cardiff and Exeter University, as well as external stakeholders from charities, patient groups, the NHS, government departments, and the United Nations Population Fund (UNFPA). |
Impact | We have run several workshops, including a three day in-person grant writing retreat. We have developed and submitted four grant applications for further funding. |
Start Year | 2021 |
Description | 4M consortium |
Organisation | University of Exeter |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Gemma Sharp established the Menarche, Menstruation, Menopause and Mental health (4M) consortium using funding from the GW4 Alliance (generator award: £14800). The consortium brings together researchers from different disciplines and institutions, with a shared interest in the intersection of menstrual and mental health. This includes researchers interested in using molecular epidemiological approaches to conduct research in this area. |
Collaborator Contribution | The 4M consortium includes partners from Bath, Cardiff and Exeter University, as well as external stakeholders from charities, patient groups, the NHS, government departments, and the United Nations Population Fund (UNFPA). |
Impact | We have run several workshops, including a three day in-person grant writing retreat. We have developed and submitted four grant applications for further funding. |
Start Year | 2021 |
Description | NutriPROGRAM consortium collaboration |
Organisation | Barcelona Institute for Global Health |
Country | Spain |
Sector | Multiple |
PI Contribution | We co-designed and lead work package 4 in the Nutriprogram consortium project. We also lead or contribute to several other activities in other work packages. |
Collaborator Contribution | Other partners lead other work packages and contribute data and results to the work package we lead (WP4). |
Impact | A collaboration agreement (including DTA) has been signed by all contributing members. The collaboration is multi-disciplinary, involving epidemiologists, geneticists, nutritionists, biologists and clinicians. |
Start Year | 2019 |
Description | NutriPROGRAM consortium collaboration |
Organisation | Erasmus MC |
Country | Netherlands |
Sector | Hospitals |
PI Contribution | We co-designed and lead work package 4 in the Nutriprogram consortium project. We also lead or contribute to several other activities in other work packages. |
Collaborator Contribution | Other partners lead other work packages and contribute data and results to the work package we lead (WP4). |
Impact | A collaboration agreement (including DTA) has been signed by all contributing members. The collaboration is multi-disciplinary, involving epidemiologists, geneticists, nutritionists, biologists and clinicians. |
Start Year | 2019 |
Description | NutriPROGRAM consortium collaboration |
Organisation | Ludwig Maximilian University of Munich (LMU Munich) |
Country | Germany |
Sector | Academic/University |
PI Contribution | We co-designed and lead work package 4 in the Nutriprogram consortium project. We also lead or contribute to several other activities in other work packages. |
Collaborator Contribution | Other partners lead other work packages and contribute data and results to the work package we lead (WP4). |
Impact | A collaboration agreement (including DTA) has been signed by all contributing members. The collaboration is multi-disciplinary, involving epidemiologists, geneticists, nutritionists, biologists and clinicians. |
Start Year | 2019 |
Description | NutriPROGRAM consortium collaboration |
Organisation | University of British Columbia |
Country | Canada |
Sector | Academic/University |
PI Contribution | We co-designed and lead work package 4 in the Nutriprogram consortium project. We also lead or contribute to several other activities in other work packages. |
Collaborator Contribution | Other partners lead other work packages and contribute data and results to the work package we lead (WP4). |
Impact | A collaboration agreement (including DTA) has been signed by all contributing members. The collaboration is multi-disciplinary, involving epidemiologists, geneticists, nutritionists, biologists and clinicians. |
Start Year | 2019 |
Description | NutriPROGRAM consortium collaboration |
Organisation | Wageningen University & Research |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | We co-designed and lead work package 4 in the Nutriprogram consortium project. We also lead or contribute to several other activities in other work packages. |
Collaborator Contribution | Other partners lead other work packages and contribute data and results to the work package we lead (WP4). |
Impact | A collaboration agreement (including DTA) has been signed by all contributing members. The collaboration is multi-disciplinary, involving epidemiologists, geneticists, nutritionists, biologists and clinicians. |
Start Year | 2019 |
Description | Pregnancy and Childhood Epigenetics (PACE) consortium |
Organisation | National Institute of Environmental Health Sciences |
Department | Pregnancy And Childhood Epigenetics Consortium |
Country | United States |
Sector | Public |
PI Contribution | I gave an invited talk at the annual PACE meeting in Rotterdam in August 2019. In the talk, I explained how the PACE consortium and its partners could use a technique (Mendelian randomisation) to explore causality in epigenetic epidemiological studies. I am also leading a PACE consortium paper about paternal BMI, which will be submitted soon. Prior to any current awards, I have led and contributed to multiple PACE projects. |
Collaborator Contribution | The PACE consortium facilitates my research on prenatal influences on offspring health. PACE is facilitating NutriPROGRAM projects on breastfeeding, maternal nutrition and offspring fat mass index and lipids. |
Impact | Several papers (before any current awards) and conference presentations. |
Start Year | 2014 |
Description | Collaboration with the Institute for Research In Schools |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | I worked with IRIS (the institute for research in schools) to inform on the design of lesson plans around COVID-19 epidemiological research. One of the lessons was focussed on collaboration in epidemiology and the different career paths in the field. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | Creative Reactions 2019 |
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 | I took part in Creative Reactions, an initiative that pairs scientists with artists to create artwork based on their academic research. I was paired with Olga Trevisan, an artist based in Venice, Italy. Based on some of my research around the Developmental Origins of Health and Disease, Olga created a piece called Beyond Question, which comments on the complexities of scientific data collection, bias and interpretation. Interesting conversations with people viewing the artwork revealed that some people's opinions (about the importance of the maternal contribution to offspring health, relative to paternal and wider societal influences) were challenged and changed. The artwork was displayed at two exhibitions at different sites in Bristol, with two separate launch events attended by the local media. |
Year(s) Of Engagement Activity | 2019 |
URL | https://epoch.blogs.bristol.ac.uk/2019/12/21/beyond-question-a-collaboration-between-epoch-and-artis... |
Description | NutriPROGRAM Twitter |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | We have a NutriPROGRAM Twitter account with nearly 50 followers. |
Year(s) Of Engagement Activity | 2019 |
URL | https://twitter.com/nutriprogram |
Description | Pint of Science talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Around 50 people attended a public talk in a pub in Bristol as part of the Pint of Science initiative. It sparked questions and discussion afterwards, and several attendees asked how they could be involved in future research. |
Year(s) Of Engagement Activity | 2022 |