Nutritional Genetics

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Health outcomes in poor populations where infection and malnutrition still intersect, are influenced by a network of interacting genetic and environmental causal factors. Our Nutritional Genetics theme, linking in with the other research themes, employs genetic and epigenetic tools at a genome-wide scale to explore critical pathways that underpin or modulate nutritionally-mediated health and disease outcomes.
We seek to understand the answers to the following questions: Does our genetic profile determine growth trajectories of children going up under a double burden of malnutrition and infectious diseases? Does maternal nutrition during early pregnancy mediate changes in gene regulation in their offspring? Does variation in genes regulating iron metabolism affect the response to infectious pathogens and/or susceptibility to anemia?

Technical Summary

Nutritional genetics covers research on the role of genetic variation on dietary responses as well as evolutionary aspects of nutritional regulation of gene expression. We employ genetic and epigenetic tools to explore critical pathways that underpin or modulate nutritionally-mediated health and disease outcomes. The key driver of the Nutritional Genetics theme within the ING is the need to provide mechanistic insights into the underlying processes.
The Keneba Biobank, a repository of biological samples involving the whole of the rural population of West Kiang (N~12000), presents a resource and major platform for our genetic research. Due to its tight integration across the other ING areas of research, Nutritional Genetics is a cross-cutting theme; we concentrate on the following two sub-themes:
1) Genetics and epigenetics of growth and development.
Over several decades our group has collected DNA, birth size and child growth records on individuals living in rural Gambia. This is being used to understand which genes affect growth trajectories employing multi-generational, cross-sectional and longitudinal study designs in combination with high-throughput genome-wide association study (GWAS) and ExomeSNPChip genotyping arrays.
Our epigenetics studies test the hypothesis that differences in maternal nutritional status during the periconceptional period influences the establishment of epigenetic signatures in the next generation. Our results on pre-natal supplementation and seasonal differences in dietary intakes demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic DNA methylation changes in their offspring postnatally.
2) Genetics of nutrition-mediated infection.
Our past and ongoing research demonstrated that viral, bacterial and host genetic factors modulate iron homeostasis and hence the pathogenesis of infectious diseases. Our future work focuses on seeking to identify genetic variants that affect phenotype variations of iron absorption and metabolism in Gambians. Risk alleles associated with iron deficiency and anemia will be ascertained in a first stage and in a second stage their potential functional effects on phenotypic outcomes including infection will be evaluated.
 
Description BMGF Discovery Expert Group
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact As a member of the BMGF Discovery Expert Group I influence policy regarding global health research policies.
 
Description Chairman - Strategic Advisory Board American Society of Nutrition
Geographic Reach North America 
Policy Influence Type Participation in a advisory committee
Impact Planning the ASN's future for Vision 2028
 
Description INSPIRE
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
 
Description Iron and Malaria Research Review
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
 
Description NIH/NICHD/Gates Technical Working Group
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
 
Description Wellcome Trust ERG 6
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact Deliberates on research funding with direct health outputs
 
Description 5 Gates Grand Challenges Explorations
Amount $100,000 (USD)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2012 
End 01/2013
 
Description Newton Fund MRC Joint Research Programme: Women's and Children's Health
Amount £928,853 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2015 
End 06/2018
 
Description Unsolicited aproach
Amount $350,000 (USD)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 06/2015 
End 06/2017
 
Title Banked DNA 
Description DNA and phenotype data from multiple cohorts in Gambia and Zanzibar. 
Type Of Material Biological samples 
Year Produced 2008 
Provided To Others? Yes  
Impact Basis of collaborations and publications 
 
Title ENID Platform 
Description The Early Nutrition and Immune Development Study recruits pregnant women throughout West Kiang. 
Type Of Material Biological samples 
Year Produced 2009 
Provided To Others? Yes  
Impact THis platform is highly productive in terms of 'add-on' studies. 
 
Title Keneba Biobank 
Description We are collecting DNA and biological samples from 12,000+ individuals in the West Kiang region of Gambia and banking these as the basis of numerous of our research projects 
Type Of Material Biological samples 
Year Produced 2011 
Provided To Others? Yes  
Impact The materials have already contributed to many research studies and are currently proving to be a very positive influence on drawing new collaborations and research funds to our group. 
 
Title West Kiang DSS 
Description Demographic Surveilance System for West Kiang Region 
Type Of Material Biological samples 
Year Produced 2015 
Provided To Others? Yes  
Impact Forms the platform for all studies we conduct and creates novel research findings through secondary analyses. 
 
Title Submission of epigenomic data to public databases 
Description We upload all our epigenetic analyses to public databases 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Not yet known 
 
Description Aflatoxin studies 
Organisation International Agency for Research on Cancer (IARC)
Country France 
Sector Public 
PI Contribution Provision of study site and samples
Collaborator Contribution IARC - epigenetic analysis UoL/QUB - aflatoxin analyses
Impact None yet
Start Year 2011
 
Description Aflatoxin studies 
Organisation Queen's University Belfast
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of study site and samples
Collaborator Contribution IARC - epigenetic analysis UoL/QUB - aflatoxin analyses
Impact None yet
Start Year 2011
 
Description Aflatoxin studies 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of study site and samples
Collaborator Contribution IARC - epigenetic analysis UoL/QUB - aflatoxin analyses
Impact None yet
Start Year 2011
 
Description African Partnership for Chronic Disease / H3Africa 
Organisation H3Africa
Country United States 
Sector Charity/Non Profit 
PI Contribution Participation in Research partnership to assess the burden and aetiology of non-communicable diseases (NCDs) in sub-Saharan Africa (SSA), with a focus on genetic epidemiology
Collaborator Contribution Coordination of research projects across multiple sites, provision of a platform for interventional research in NCDs, ensureing that African populations benefit from the ongoing advances in genomics.
Impact None yet
Start Year 2012
 
Description African Partnership for Chronic Disease / H3Africa 
Organisation University of Cambridge
Department Department of Public Health and Primary Care
Country United Kingdom 
Sector Academic/University 
PI Contribution Participation in Research partnership to assess the burden and aetiology of non-communicable diseases (NCDs) in sub-Saharan Africa (SSA), with a focus on genetic epidemiology
Collaborator Contribution Coordination of research projects across multiple sites, provision of a platform for interventional research in NCDs, ensureing that African populations benefit from the ongoing advances in genomics.
Impact None yet
Start Year 2012
 
Description African Partnership for Chronic Disease / H3Africa 
Organisation University of the Gambia
Country Gambia 
Sector Academic/University 
PI Contribution Participation in Research partnership to assess the burden and aetiology of non-communicable diseases (NCDs) in sub-Saharan Africa (SSA), with a focus on genetic epidemiology
Collaborator Contribution Coordination of research projects across multiple sites, provision of a platform for interventional research in NCDs, ensureing that African populations benefit from the ongoing advances in genomics.
Impact None yet
Start Year 2012
 
Description Choline and brain function 
Organisation University of North Carolina at Chapel Hill
Country United States 
Sector Academic/University 
PI Contribution Piloting of EEG methods for assessing brain function for ultimate implementation in choline supplement trial. DNA samples for assessment of variation in one-carbon genes in Gambians.
Collaborator Contribution Expertise and equipment. Genotyping of Gambian DNA samples.
Impact None yet
Start Year 2012
 
Description Epigenetic studies 
Organisation Baylor College of Medicine
Country United States 
Sector Hospitals 
PI Contribution These partners contribute to a research network at which we are at the centre.
Collaborator Contribution UBC- biomarker analyses BCM - epiallele analyses UNC - food analyses UoC - epigenome profiling IARC - epigenome profiling UoL+QUoB - aflatoxin analysis
Impact Publications and new knowledge. 21203497 22124338 22307237 22267336 23576045
Start Year 2008
 
Description Epigenetic studies 
Organisation International Agency for Research on Cancer (IARC)
Country France 
Sector Public 
PI Contribution These partners contribute to a research network at which we are at the centre.
Collaborator Contribution UBC- biomarker analyses BCM - epiallele analyses UNC - food analyses UoC - epigenome profiling IARC - epigenome profiling UoL+QUoB - aflatoxin analysis
Impact Publications and new knowledge. 21203497 22124338 22307237 22267336 23576045
Start Year 2008
 
Description Epigenetic studies 
Organisation Queen's University Belfast
Country United Kingdom 
Sector Academic/University 
PI Contribution These partners contribute to a research network at which we are at the centre.
Collaborator Contribution UBC- biomarker analyses BCM - epiallele analyses UNC - food analyses UoC - epigenome profiling IARC - epigenome profiling UoL+QUoB - aflatoxin analysis
Impact Publications and new knowledge. 21203497 22124338 22307237 22267336 23576045
Start Year 2008
 
Description Epigenetic studies 
Organisation University of British Columbia
Country Canada 
Sector Academic/University 
PI Contribution These partners contribute to a research network at which we are at the centre.
Collaborator Contribution UBC- biomarker analyses BCM - epiallele analyses UNC - food analyses UoC - epigenome profiling IARC - epigenome profiling UoL+QUoB - aflatoxin analysis
Impact Publications and new knowledge. 21203497 22124338 22307237 22267336 23576045
Start Year 2008
 
Description Epigenetic studies 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution These partners contribute to a research network at which we are at the centre.
Collaborator Contribution UBC- biomarker analyses BCM - epiallele analyses UNC - food analyses UoC - epigenome profiling IARC - epigenome profiling UoL+QUoB - aflatoxin analysis
Impact Publications and new knowledge. 21203497 22124338 22307237 22267336 23576045
Start Year 2008
 
Description Epigenetic studies 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution These partners contribute to a research network at which we are at the centre.
Collaborator Contribution UBC- biomarker analyses BCM - epiallele analyses UNC - food analyses UoC - epigenome profiling IARC - epigenome profiling UoL+QUoB - aflatoxin analysis
Impact Publications and new knowledge. 21203497 22124338 22307237 22267336 23576045
Start Year 2008
 
Description Epigenetic studies 
Organisation University of North Carolina at Chapel Hill
Country United States 
Sector Academic/University 
PI Contribution These partners contribute to a research network at which we are at the centre.
Collaborator Contribution UBC- biomarker analyses BCM - epiallele analyses UNC - food analyses UoC - epigenome profiling IARC - epigenome profiling UoL+QUoB - aflatoxin analysis
Impact Publications and new knowledge. 21203497 22124338 22307237 22267336 23576045
Start Year 2008
 
Description Epigenetics and telomere length 
Organisation University College London
Department Institute of Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution We provide the research setting and samples and hypotheses.
Collaborator Contribution Dr Jess Buxton brings expertise and methods training.
Impact None yet.
Start Year 2015
 
Description Gambian National Nutrition Agency (NaNA) 
Organisation Government of The Gambia
Department National Nutrition Agency (NaNA) Gambia
Country Gambia 
Sector Public 
PI Contribution We support NaNA in numerous ways, mostly related to staff training.
Collaborator Contribution Through quarterly meetings NaNA assist us with advice about Gambian Government priorities in nutrition. They also help facilitate short-term deviations from standard government policy necessary fro certain trials.
Impact The positive and cordial relationships between MRC and NaNA over many years represent a notable output.
 
Description Genes-in-action iron 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Health Services Research and Policy
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of field samples and opportunities
Collaborator Contribution Co-supervsion of PhD student
Impact None yet.
Start Year 2016
 
Description Genetics of growth 
Organisation Early Growth Genetics Consortium (EGG)
Country United Kingdom 
Sector Private 
PI Contribution Provision of DNA and anthropometric data for up to 3500 individuals. Joint analysis of results.
Collaborator Contribution Analysis of gene variation in genes involved in growth and development, including bone health
Impact 19434426 19265514 18852700 21831878 22896641 23202124 23246670
Start Year 2006
 
Description Genetics of growth 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Unit
Country United Kingdom 
Sector Public 
PI Contribution Provision of DNA and anthropometric data for up to 3500 individuals. Joint analysis of results.
Collaborator Contribution Analysis of gene variation in genes involved in growth and development, including bone health
Impact 19434426 19265514 18852700 21831878 22896641 23202124 23246670
Start Year 2006
 
Description Genetics of growth 
Organisation University of Cambridge
Department Department of Paediatrics
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of DNA and anthropometric data for up to 3500 individuals. Joint analysis of results.
Collaborator Contribution Analysis of gene variation in genes involved in growth and development, including bone health
Impact 19434426 19265514 18852700 21831878 22896641 23202124 23246670
Start Year 2006
 
Description Genetics of growth 
Organisation University of Exeter
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of DNA and anthropometric data for up to 3500 individuals. Joint analysis of results.
Collaborator Contribution Analysis of gene variation in genes involved in growth and development, including bone health
Impact 19434426 19265514 18852700 21831878 22896641 23202124 23246670
Start Year 2006
 
Description Genetics of infection and immunity 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution DNA sample and data provision in relation to HIV, TB, malaria, SCD, HBV and MenC studies.
Collaborator Contribution Genotyping and joint analyses
Impact Formation of HIGH consortium; 19474129 18716131 18291005 20552021 20970823 20806065 19793845 20924289 21595648 21459787 21939508 21068433 22205660 23691341 23753024 21993677
 
Description Genetics of infection and immunity 
Organisation Medical Research Council (MRC)
Department MRC Unit, The Gambia
Country Gambia 
Sector Public 
PI Contribution DNA sample and data provision in relation to HIV, TB, malaria, SCD, HBV and MenC studies.
Collaborator Contribution Genotyping and joint analyses
Impact Formation of HIGH consortium; 19474129 18716131 18291005 20552021 20970823 20806065 19793845 20924289 21595648 21459787 21939508 21068433 22205660 23691341 23753024 21993677
 
Description Genetics of infection and immunity 
Organisation San Pietro Hospital
Country Italy 
Sector Hospitals 
PI Contribution DNA sample and data provision in relation to HIV, TB, malaria, SCD, HBV and MenC studies.
Collaborator Contribution Genotyping and joint analyses
Impact Formation of HIGH consortium; 19474129 18716131 18291005 20552021 20970823 20806065 19793845 20924289 21595648 21459787 21939508 21068433 22205660 23691341 23753024 21993677
 
Description Genetics of infection and immunity 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution DNA sample and data provision in relation to HIV, TB, malaria, SCD, HBV and MenC studies.
Collaborator Contribution Genotyping and joint analyses
Impact Formation of HIGH consortium; 19474129 18716131 18291005 20552021 20970823 20806065 19793845 20924289 21595648 21459787 21939508 21068433 22205660 23691341 23753024 21993677
 
Description Genetics of infection and immunity 
Organisation Vanderbilt University
Country United States 
Sector Academic/University 
PI Contribution DNA sample and data provision in relation to HIV, TB, malaria, SCD, HBV and MenC studies.
Collaborator Contribution Genotyping and joint analyses
Impact Formation of HIGH consortium; 19474129 18716131 18291005 20552021 20970823 20806065 19793845 20924289 21595648 21459787 21939508 21068433 22205660 23691341 23753024 21993677
 
Description Genetics of malnutrition 
Organisation University of Virginia (UVa)
Department Department of Pediatrics
Country United States 
Sector Hospitals 
PI Contribution Provision of DNA and anthropometric data on 1500 Gambians
Collaborator Contribution GWAS and ExomeChip genotyping
Impact None yet
Start Year 2011
 
Description Hormonal control of growth 
Organisation University of Colorado Boulder
Country United States 
Sector Academic/University 
PI Contribution Detailed studies of hormonal regulation of growth will be performed at MRC Keneba
Collaborator Contribution Robin Bernstein at UC is the PI on the grant funding this research project.
Impact None yet.
Start Year 2012
 
Description Maternal nutrition and offspring miRNAs 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution We provide the research setting, samples and manpower. We sought and successfully achieved additional funds from the Bill Melinda Gates Foundation to support this work.
Collaborator Contribution Dr Sarah Finer at QMUL brings expertise in miRNA programming an training in lab methods.
Impact None yet.
Start Year 2015
 
Description POMC collaboration 
Organisation Charité - University of Medicine Berlin
Country Germany 
Sector Academic/University 
PI Contribution Provision of SoC data to add to analysis and publications
Collaborator Contribution Comparative data and analysis on POMC methylation and obesity
Impact Publications have been listed
Start Year 2016
 
Title KEMRes 
Description Keneba Electronic Medical Registration System 
Type Support Tool - For Medical Intervention
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2011
Development Status Under active development/distribution
Impact KEMReS forms a vital part of our research patient selection as well as providing improved care fro our patient population. 
 
Description BBC documentary 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact We featured prominently in the BBC 2 documentary: 'Countdown to Life: The Extraordinary Making of You'
Year(s) Of Engagement Activity 2015
URL http://www.bbc.co.uk/programmes/b06crff1
 
Description ING website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact ING now has it's own website, where key news items are posted regularly.

The website is a vital point of information to ING's research activities.
Year(s) Of Engagement Activity 2012
 
Description International press coverage 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Following a press release we achieved worldwide media coverage for our latest epigenetic studies.
Year(s) Of Engagement Activity 2015
URL http://ing.mrc.ac.uk/home/news/
 
Description MRC Centenary Events @ UCL 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact 500 attendees across a wide range of the public plus other academics

Wider interest and knowledge of MRC activities
Year(s) Of Engagement Activity 2013
 
Description MRC Festival 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact MRC Festival is an Annual Showcase of MRC Unit The Gambia's activities
Year(s) Of Engagement Activity 2016
 
Description MRC UCL Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact ING participated in the UCL Centenary event, targeted at the general public but also including scientists from other MRC Units and groups in London. ING contribution included a formal lecture by Prof Prentice plus stands and exhibitions highlighting our work in Keneba.

Publicity in local London area.
Year(s) Of Engagement Activity 2013
 
Description Open Day (Gambia) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact Open Day in Keneba
Year(s) Of Engagement Activity 2016
 
Description Open days 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Open day

Continued good relations with surrounding villagers who participate in our research
Year(s) Of Engagement Activity 2007,2008,2013,2014
 
Description Podcast 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Contribution to podcast

Multiple
Year(s) Of Engagement Activity 2009,2014
 
Description Public lecture 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Open Lecture to general audience including politicians

Improved profile
Year(s) Of Engagement Activity 2008,2013
 
Description Radio interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact BBC World Service interview

None.
Year(s) Of Engagement Activity 2009,2014
 
Description Tama - article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Article

None known
Year(s) Of Engagement Activity 2008,2014