London School of Hygiene & Tropical Medicine

The Unit has joined a consortium of 20 research groups from around the world that aims to improve global health by uncovering the effects of genomic and environmental diversity on differences in disease risk observed across the global populations, including Uganda.

The Unit contributes to the consortium by providing samples from our rich Uganda Genome Resource for genetic and environmental determinants of DNA methylation variation. The Uganda Genome Resource, which was generated from the Unit’s General Population Cohort, has up to 22,000 study participants from different African ethnic groups. This data will aid the study in understanding of disease discordance and differences in risk factors between ancestries.

Dr Segun Fatumo, head of non-communicable diseases (NCD) genomics studies at the Unit and a collaborator on the Diverse Epigenetic Epidemiology Partnership (DEEP) study, said

"Today, we embark on a transformative journey in epigenomics, one that celebrates the rich diversity of the human tapestry. The Diverse Epigenetic Epidemiology Partnership (DEEP) study is a beacon of progress, recognizing that understanding the complexity of human health necessitates representation from every corner of the globe. As we embark on this groundbreaking five-year project, we are really excited to see the inclusion of African cohorts including those from Uganda in this study recognizing the immense genetic diversity that resides within this continent.”

The groundbreaking five-year project, led by researchers in the University of Bristol, the MRC Unit The Gambia at London School of Hygiene & Tropical Medicine and the CSIR Centre for Cellular and Molecular Biology in India, will explore key population health questions using datasets from across African, Asian, and North and South American continents.

The Diverse Epigenetic Epidemiology Partnership (DEEP) study, funded by the Medical Research Council, will generate genomic datasets in underrepresented populations.  The DEEP study will develop software and infrastructure and conduct advanced statistical analyses to build new resources. These new resources will sit alongside international health and genetics databases to look at trends in variation in DNA methylation - a process where chemical groups attach to DNA in order to help to turn genes on and off.

Levels of DNA methylation differ from one person to another and are influenced by both genetic makeup and environmental factors. Differences in DNA methylation patterns are critical factors associated with a range of measures of health and disease. By analysing DNA methylation data and health-related measures from people around world, the DEEP study aims to identify causes and mechanisms of these health outcomes.

There is huge variation in disease onset and symptoms for people living in different global regions. Much of the population health research conducted to date has drawn heavily on data collected from people of white European origins. This means that many global communities are often under-represented in health studies and the important effects of genetic and environmental diversity on health within those communities can be missed, for example the huge genetic diversity across Africa.

The DEEP study researchers aim to bridge this gap by studying individuals representing diverse genetic and environmental contexts and learn which DNA methylation patterns contribute to their disease risk in each context. This research will enable identification of disease-causing mechanisms that are common worldwide and those which are unique to particular groups or regions. It will help with answering questions such as whether medicines developed in one part of the world will be effective for all. Ultimately the DEEP study hopes to enable targeted interventions or treatments and reduce global health disparity and inequity.

Dr Josine Min, Research Fellow in Genetic and Epigenetic Epidemiology at the MRC Integrative Epidemiology Unit (MRC IEU) at the University of Bristol, and joint project lead, said: ”Current DNA databases are mainly European. Genetic databases for genomic research need diversity to help all people and to get a better understanding of which factors are causing differences in gene regulation and therefore differences in disease risk.”

Dr Hannah Elliott, Research Fellow in Epidemiology in the MRC IEU at the University of Bristol, and joint project lead, added: “This project will vastly expand our current knowledge about DNA methylation variation and human health. Key to our project’s success is equitable collaboration between our project partners worldwide.

“It is really important to work with partners who understand health in their respective cohorts and who are able to effectively share results back with the local communities who have donated their DNA.”

Dr Giriraj Chandak, Sir J C Bose Fellow at the CSIR Centre for Cellular and Molecular Biology, India, and co-investigator, explained: “This collaborative study involving scientists with varied expertise provides a unique opportunity to understand gene-gene and gene-environment interaction and their role in intermediate traits associated with non-communicable diseases or the disease itself.

“I am very excited at the inclusion of Indian cohorts, (representing a sixth of the world population) with longitudinal data on subjects making it possible to draw causal inferences, in association with the trans-ancestry cohorts.”

Dr Prachand Issarapu, Research Fellow in Bioinformatics at the MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, UK and The Gambia, and co-investigator, said: “Understanding disease pathways that resonate across populations is key to crafting universally effective medicine. The DEEP study will unravel both population-specific and pan-ancestry (epi)genetic underpinnings, offering crucial insights into the determinants of human health and disease.”

The project will initially focus on early-life health, which is a particular interest to the partners in Africa, and cardiovascular health, which is important to the partners in India.

The project welcomes participation from additional partners who have collected DNA methylation and genetic data.

. . . ENDS

Notes to editors:

To arrange an interview with Dr. Segun Fatumo please contact the Unit press office at press@mrcuganda.org

For more project information contact Joanne Fryer [Mon to Wed], email joanne.fryer@bristol.ac.uk, mobile: +44 (0)7747 768805 or Caroline Clancy [Wed to Fri], email caroline.clancy@bristol.ac.uk, mobile: +44 (0)7776 170238 at the University of Bristol Press Office.

About the Diverse Epigenetic Epidemiology Partnership (DEEP) study

The Diverse Epigenetic Epidemiology Partnership (DEEP) study is a five-year project funded by the UK’s Medical Research Council. The project is led by researchers at MRC Integrative Epidemiology Unit at the University of Bristol, UK, with co-investigators at CSIR Centre for Cellular and Molecular Biology, India and MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, UK and The Gambia.

Other current partners are from: Academic Medical Centre, Amsterdam (AMC), The Netherlands; Centre for Cancer Epidemiology, Tata Memorial Centre, India; Columbia University, USA; Hamad Bin Khalifa University, Qatar; Harvard School of Public Health, USA; MRC/UVRI and LSHTM Uganda Research Unit;  National Center for Epidemiology, Instituto de Salud Carlos III, Spain; National Institutes of Health (NIH), USA; North-West University, South Africa; Pasteur Institute and Collège de France, France; Peking University Health Science Centre, China; Stanford University, USA; St Vincent's Institute of Medical Research, Australia; Translational Genomics Research Institute; TGen, USA; Universidade Federal de Pelotas, Brazil; Universite Cheikh Anta Diop de Dakar, Senegal; University of Chicago, USA; University of Tokushima, Japan; and Vanderbilt University Medical Center, USA.

About the MRC Integrative Epidemiology Unit (IEU)
The MRC Integrative Epidemiology Unit (IEU) at the University of Bristol conducts some of the UK's most advanced population health science research. It uses genetics, population data and experimental interventions to look for the underlying causes of chronic disease. The unit exploits the latest advances in genetic and epigenetic technologies. They develop new analytic methods to improve our understanding of how our family background behaviours and genes interact to influence health outcomes.

About the Medical Research Council

The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-three MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. www.ukri.org/councils/mrc/

The MRC/UVRI & LSHTM Uganda Research Unit is an internationally recognized centre of excellence for research and training. Established in 1988, our mission is to conduct high-quality research that adds knowledge and leads to improved control of infectious and non-communicable diseases in Uganda, Africa and globally, through translation of scientific findings into policy and practice, and rigorous research capacity building. The Unit is one of two (2) UKRI/MRC Units outside the UK, the other one in the Gambia. With strong affiliation to the Uganda Virus Research Institute (UVRI), the Unit enjoys vital representation at government level, which facilitates translation of research findings. In 2018, the Unit was transferred to LSHTM, a major UK global health institution. This new partnership is boosting research capacity into some of the current and emerging health issues in Africa and globally. www.mrcuganda.org

Issued by the University of Bristol media team