Creating a West African BioResource for Nutritional Genetics and Epigenetics
Lead Research Organisation:
London School of Hygiene and Tropical Medicine
Abstract
The Nutrition Theme at MRC Unit The Gambia will partner with a broad team of collaborators in Bristol (Bristol University and MRC Integrative Epidemiology Unit) to create a new West African BioResource (WABR). The new bioresource will consist of rich nutritional cohorts, databases and the Keneba Biobank constructed over decades of research in the West Kiang area of rural Gambia. These will be made open access to worldwide collaborators to support novel research methods to better understand the complex relationships between diet, nutritional status and infectious and non-communicable diseases. The new methodologies will be strongly based on a genes-in-action (alternatively known as recall-by-genotype) paradigm that allows investigators to research the impact of genetic and epigenetic variants on health with highly efficient studies using small numbers of participants. Based upon the Bristol group's world-leading processes we will conduct a 'clone and adapt' exercise to bring the Gambian bioresource up to the same world standard. This process will be extended to the biobanks at MRCG Fajara and at our West African Global Health Alliance (WAGHA) partner institute IRESSEF in Dakar. We will also prepare a bioresource toolkit that can be accessed by other institutes with cohorts and biobanks in other LMICs.
Technical Summary
Global open access to research is strongly encouraged as a means to maximise the return on investments for investigators, participants in medical research and funders. Based on an extraordinarily rich set of nutritional cohorts, databases and the Keneba Biobank we will team up with researchers in Bristol to 'professionalise and externalise' these resources with a special emphasis on driving new collaborations using our genes-in-action (recall-by-genotype) paradigm that allows highly efficient research on the impact of genetic and epigenetic variants on nutritionally-mediated disease processes. The initial work based around the cohorts led by the Nutrition Theme at MRCG will be extended first to additional biobanks at MRCG Fajara and at IRESSEF Dakar through our the West African Global Health Alliance (WAGHA). We will additionally create a toolbox that can be adapted for uptake by other LMIC institutions.
Planned Impact
Progress in developing next-generation nutritional interventions is still greatly hampered by serious gaps in our understanding of mechanisms underlying complex diet/disease interactions. Progress in this field can be accelerated a) by a greater sharing of cohorts, databases and biobanks internationally in order to bring the best minds to bear on the problems, and b) by developing novel research methods. Creation of the proposed West African BioResource (WABR) will take a major step in this direction by promoting international open access to the unique nutritional resources collected over many decades at MRCG Keneba. These processes will be immediately cloned to MRCG Fajara and IRESSEF Dakar and a transportable toolkit will be offered for uptake by other institutions in LMICs. We anticipate that this process will make an important contribution to accelerating discovery science in the field of nutrition and beyond.
Organisations
- London School of Hygiene and Tropical Medicine (Lead Research Organisation)
- Charité - University of Medicine Berlin (Collaboration)
- Kenyan Institute for Medical Research (KEMRI) (Collaboration)
- London School of Hygiene and Tropical Medicine (LSHTM) (Collaboration)
- University College London (Collaboration)
- University of Bristol (Collaboration)
People |
ORCID iD |
Publications
Saffari A
(2018)
Estimation of a significance threshold for epigenome-wide association studies.
in Genetic epidemiology
Corbin LJ
(2018)
Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference.
in Nature communications
Muriuki JM
(2019)
The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia.
in Science advances
Benjamin-Chung J
(2020)
Early childhood linear growth faltering in low- and middle-income countries
Surendran P
(2020)
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.
in Nature genetics
Jallow MW
(2020)
Differences in the frequency of genetic variants associated with iron imbalance among global populations.
in PloS one
Abuga KM
(2020)
Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children.
in Wellcome open research
Muriuki JM
(2020)
Estimating the burden of iron deficiency among African children.
in BMC medicine
Maasen K
(2020)
Periconceptional environment predicts leukocyte telomere length in a cross-sectional study of 7-9 year old rural Gambian children.
in Scientific reports
Saffari A
(2020)
Effect of maternal preconceptional and pregnancy micronutrient interventions on children's DNA methylation: Findings from the EMPHASIS study.
in The American journal of clinical nutrition
Pace RM
(2021)
Variation in Human Milk Composition Is Related to Differences in Milk and Infant Fecal Microbial Communities.
in Microorganisms
Ruiz L
(2021)
Comparison of Two Approaches for the Metataxonomic Analysis of the Human Milk Microbiome.
in Frontiers in cellular and infection microbiology
Jallow MW
(2021)
Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians.
in Scientific reports
Okala SG
(2021)
Seasonal modulation of antibody response to diphtheria-tetanus-pertussis vaccination in infants: a cohort study in rural Gambia.
in BMC public health
Mogire RM
(2021)
Prevalence and predictors of vitamin D deficiency in young African children.
in BMC medicine
Ghantous A
(2021)
Aflatoxin Exposure during Early Life Is Associated with Differential DNA Methylation in Two-Year-Old Gambian Children.
in International journal of molecular sciences
Williams J
(2021)
Key genetic variants associated with variation of milk oligosaccharides from diverse human populations
in Genomics
Candler T
(2021)
DNA methylation at a nutritionally sensitive region of the PAX8 gene is associated with thyroid volume and function in Gambian children.
in Science advances
Jallow MW
(2021)
Common Variants in the TMPRSS6 Gene Alter Hepcidin but not Plasma Iron in Response to Oral Iron in Healthy Gambian Adults: A Recall-by-Genotype Study.
in Current developments in nutrition
Muriuki JM
(2021)
Malaria is a cause of iron deficiency in African children.
in Nature medicine
Nabwera HM
(2021)
Stunting of Growth in Developing Countries.
in World review of nutrition and dietetics
Gonzales GB
(2021)
Plasma lipids and growth faltering: A longitudinal cohort study in rural Gambian children.
in Science advances
Liu E
(2022)
Effects of prenatal nutritional supplements on gestational weight gain in low- and middle-income countries: a meta-analysis of individual participant data.
in The American journal of clinical nutrition
Perumal N
(2022)
Implications for quantifying early life growth trajectories of term-born infants using INTERGROWTH-21st newborn size standards at birth in conjunction with World Health Organization child growth standards in the postnatal period.
in Paediatric and perinatal epidemiology
Silver MJ
(2022)
Environmentally sensitive hotspots in the methylome of the early human embryo.
in eLife
Mogire RM
(2022)
Vitamin D Deficiency and Its Association with Iron Deficiency in African Children.
in Nutrients
Bourassa MW
(2022)
Thiamine deficiency in Gambian women of reproductive age.
in Annals of the New York Academy of Sciences
De Goffau MC
(2022)
Gut microbiomes from Gambian infants reveal the development of a non-industrialized Prevotella-based trophic network.
in Nature microbiology
Antoun E
(2022)
DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study.
in Clinical epigenetics
Derakhshan M
(2022)
Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo.
in Nucleic acids research
Sainty R
(2023)
The influence of early environment and micronutrient availability on developmental epigenetic programming: lessons from the placenta.
in Frontiers in cell and developmental biology
Joof F
(2023)
Genetic variations in human ATP2B4 gene alter Plasmodium falciparum in vitro growth in RBCs from Gambian adults.
in Malaria journal
Issarapu P
(2023)
DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood
in Nature Communications
Lechner L
(2023)
Early-set POMC methylation variability is accompanied by increased risk for obesity and is addressable by MC4R agonist treatment.
in Science translational medicine
Mohammed NI
(2023)
Quantifying excess mortality during the COVID-19 pandemic in 2020 in The Gambia: a time-series analysis of three health and demographic surveillance systems.
in International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
Yeung E
(2024)
Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.
in Aging cell
Derakhshan M
(2024)
Metastable epialleles in humans.
in Trends in genetics : TIG
Ambalavanan A
(2024)
Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children.
in Nature communications
Nacis JS
(2024)
Barriers and enablers to the effective implementation of omics research in low- and middle-income countries.
in Nature biotechnology
Daskeviciute D
(2025)
Non-canonical imprinting, manifesting as post-fertilization placenta-specific parent-of-origin dependent methylation, is not conserved in humans.
in Human molecular genetics
| Description | The award has enhanced our ability to share DNA, sequences and metadata leading to several new outputs and many in the pipeline. |
| Exploitation Route | The whole intention of this award is to externalise our data so as to make better use of it. |
| Sectors | Agriculture Food and Drink Pharmaceuticals and Medical Biotechnology |
| URL | https://research-information.bris.ac.uk/en/projects/harnessing-dna-methylation-variation-between-populations-to-under-2 |
| Description | FANUS Council |
| Geographic Reach | Africa |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | FANUS is the overall supervisory body for all African Nutrition Societies |
| URL | https://www.fanus.org/ |
| Description | IUNS Council |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | IUNS is the governing body for all National Nutrition Societies and thereby influences governance and outputs |
| URL | https://iuns.org/ |
| Description | LPS Enhancement |
| Amount | £475,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2021 |
| End | 03/2022 |
| Description | ALSPAC |
| Organisation | University of Bristol |
| Department | Avon Longitudinal Study of Parents and Children (ALSPAC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are collaborating with the Bristol ALSPAC team in order to 'clone and adapt' their advanced processes for use in WABR. |
| Collaborator Contribution | The ALSPAC team are advising us on optimising the set up of 'externalising' our West African BioResource to international collaborators. |
| Impact | Work in progress - none yet. |
| Start Year | 2018 |
| Description | DEEP - Diverse Epigenetic Epidemiology Partnership |
| Organisation | University of Bristol |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Co-applicants with Drs Hannah Elliott and Josine Min at Bristol and Prof Giriraj Chandak at CCMB Hyderabad |
| Collaborator Contribution | Contribution of conceptual inputs, epigenetic data and bioinformatics. |
| Impact | https://www.deep-epigenetics.org |
| Start Year | 2024 |
| Description | DEEP Consortium |
| Organisation | University of Bristol |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are co-PIs in the MRC-funded DEEP Consortium |
| Collaborator Contribution | See URL |
| Impact | None yet |
| Start Year | 2024 |
| Description | DEEP Consortium |
| Organisation | University of Bristol |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are co-PIs on the MRC-funded DEEP Consortium |
| Collaborator Contribution | Please refer to DEEP website |
| Impact | No outputs yet |
| Start Year | 2024 |
| 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 | 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 | Harnessing DNA methylation variation between populations to understand disease discordance across ancestries (MR/X021599/1) |
| Organisation | University of Bristol |
| Department | MRC Integrative Epidemiology Unit |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Provision of samples, data and analysis |
| Collaborator Contribution | Generated grant idea and obtained funding |
| Impact | none yet |
| Start Year | 2023 |
| Description | KEMRI-Kilifi collaboration |
| Organisation | Kenyan Institute for Medical Research (KEMRI) |
| Country | Kenya |
| Sector | Public |
| PI Contribution | Collaboration by way of pooling data and analysis on iron and genetics. |
| Collaborator Contribution | Publications in progress. |
| Impact | Publications in progress |
| Start Year | 2018 |
| Description | Numerous collaborations and data contributions to meta-analyses, GWAS and EWAS studies |
| Organisation | London School of Hygiene and Tropical Medicine (LSHTM) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | The KWLPS encourages access to our longitudinal data for secondary data analysis and has many outputs (listed in publications) |
| Collaborator Contribution | We have contributed data and samples to numerous national and international studies. Notable recent examples include the Gates Knowledge Integration analysis of longitudinal growth published din 3 Nature papers, our contributions to the Gestational Weight Gain project with numerous meta-analysed outputs, data contribution to the Global Cardiovascular Risk Consortium, to the ICHoR study and to several pan-African GWAS analysis and global EWAS analyses (PACE Consortium). |
| Impact | Listed under publications |
| Start Year | 2020 |
| 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 |
| Description | Multiple engagements nationally (with government stakeholders) and internationally with collaborating institutions |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Multiple engagements with local government (health) stakeholders and international collaborators |
| Year(s) Of Engagement Activity | 2020 |