1.What is the name of this project?
This project is called Human Heredity and Health in Africa, and designated H3Africa.
2.Who are the partners in this effort and what is their role?
The H3Africa Initiative is funded through a partnership between the U.S. National Institutes of Health, an agency of the U.S. Department of Health and Human Services, and the Wellcome Trust, a global charity based in London, U.K.
In the first phase of the Initiative, which ended in 2016, the NIH and Wellcome Trust committed $64 and $12 million respectively for five years. In 2016, the NIH committed another round of funding to support the Phase II of the project, which will run for another 5 years. Wellcome Trust has also committed to supporting the second phase through the African Academy of Sciences (AAS), Alliance for Accelerating Science in Africa (AESA).
Wellcome has made a £9m grant to AESA to run a second phase of the programme in partnership with the US National Institutes of Health. (NIH). The NIH will manage their awards, while AESA will be responsible for the delivery of the Phase II awards for the H3Africa initiative and will manage the H3Africa consortium in partnership with the Wellcome Trust and the NIH.
In addition, AESA has entered into a collaboration with GlaxoSmithKline (GSK) as part of the Africa NCD Open Lab initiative. Additional funding will be made available to fund projects relevant to the Open Lab’s objectives in specific sub-set countries (see call).
3.What is the goal of this project?
Organised to develop large-scale population studies by African researchers on African populations, H3Africa aims to use the new tools of genome research in combination with clinical and environmental analyses to understand the interaction of genes and the environment in health and disease. In addition, H3Africa is intended to create new research capabilities in Africa, both in terms of infrastructure and in the creation of new collaborations between African researchers and researchers in the United States, Europe, global South and elsewhere. It also intends to foster collaborations between researchers in different parts of Africa.
4.What research techniques will be used by H3Africa?
H3Africa researchers will employ a wide range of genetic and genomic tools appropriate for the studies selected for funding. Genomic tools will likely include a genomic analysis of genetic variation using genotyping arrays used in genome-wide association studies, or exome or whole genome sequencing.
Other genomic technologies, such as proteomics and metabolomics may also be applied. In addition, individual projects will carry out careful clinical analyses of study participants (blood pressure for hypertension studies, for example), as well as environmental and cultural assessments to understand non-genetic contributions to health and disease.
5.Where will the genomic and genetic tests be carried out?
Although H3Africa is intended to build capacity in Africa, it may be that studies will rely on existing genome facilities in Africa, or in partner countries such as the United States and Europe. It is anticipated that H3Africa will help develop leadership skills in genomics and that adequate genotyping and sequencing capacity will be developed in Africa.
6.Why are genetic studies being carried out on African populations?
All humans trace their heritage to Africa, where humans first evolved and then migrated around the globe. Previous studies, such as the International HapMap Project and the 1000 Genomes Project, have shown that African populations have the greatest amount of genetic variability. Genetic variation between individuals has been shown to affect the risk of developing different diseases.
By studying African populations with the greatest amount of genetic variation, especially in relation to clinical findings and environmental information, researchers expect to learn a great deal about the genetic roots of diseases that afflict Africans and other human populations across the globe.
7.What kinds of diseases will H3Africa study?
H3Africa will focus broadly on two types of diseases: communicable and non-communicable. The role of genetic variability in infectious diseases is not fully understood, so one set of studies will focus on the interactions between disease-causing micro-organisms and human hosts.
Non-communicable disease would include common disorders such as hypertension, stroke, heart disease, kidney disease, diabetes and cancer, all of which are becoming widespread in African populations. H3Africa will seek to understand the interaction between genetic susceptibilities and environmental changes – such as diet – that may be leading to the increased morbidity and mortality.
8.How many individuals would be involved in an H3Africa study?
Typically, studies that evaluate genetic predispositions for illness include a few thousand individuals. The size of the study will likely relate to the availability of samples, but should be of a sufficient scale and design to ensure that disease-causing variants can be detected. Some studies in H3Africa may involve 10,000 or more individuals.
9.Will Africans who participate in these studies derive any benefit?
Yes, Africans who participate in these studies will derive immediate and long-term benefits. Study participants will, in many cases, receive medical examinations and screening tests. If disease conditions are detected, the individual will be so advised and referred for medical care (though not necessarily provided by the study).
Long-term benefits may be derived – both in Africa and in populations around the world – from the improved understanding of disease that leads to better diagnostics and treatments.
10.What do the research leaders hope to learn from genomic and environmental studies in African countries and their populations?
H3Africa will focus on both genes and environmental data in the expectation that it will lead to an understanding of how the interaction between both influences health and disease. Environmental factors are not limited to just nutrition and pollution, but also include cultural, religious, political and other social factors that may influence health. African populations carry the oldest, most diverse set of human genes; H3Africa provides an opportunity to see how these genes behave in different environments.
11.How will the partnership be managed?
H3Africa is organised as a Consortium that brings participants together in a highly collaborative and synergistic effort. The H3Africa Consortium includes all participants of research and infrastructure projects funded through H3Africa, as well as staff from AESA, Wellcome Trust, the H3Africa Coordinating Office, H3ABIONET and the NIH.
Principal Investigator(s) work closely with funder representatives on the H3Africa Steering Committee to oversee H3Africa Consortium activities and a number of Working Groups work to develop key policies and guidelines. Successful applicants or members of their team will be expected to participate fully in all H3Africa Consortium activities and attend the twice-yearly H3Africa Consortium meetings.
12.How will the funds be distributed?
Wellcome Trust has channelled its funding through AESA while GSK will directly fund projects of interest. Wellcome Trust, AESA and GSK have established mechanisms for awarding grants, which will be employed to ensure a fair and transparent competition process for awarding research funding. GSK funded projects will be managed by AESA and are expected to conform to the overall H3Africa consortium policies and guidelines together with any additional requirements of GSK. The deadline for the NIH call for 2017 has already passed and the process of identifying potential grantees is underway.
13.What are the areas of interest for GSK and what countries can apply for the GSK funding?
GSK awards will be limited to research focused on improving the understanding of disease mechanisms, epidemiology, pathophysiology and aetiology, or prevention and treatment of primary disease and associated complications in at least one of the following priority non-communicable disease (NCD) areas: cardiovascular disease, oncology, chronic respiratory disease, chronic kidney disease and diabetes.
GSK funding will be restricted to projects led from within the following countries; Cameroon, Côte D’Ivoire, Ethiopia, Ghana, Gambia, Kenya, Malawi, Nigeria, Senegal, Tanzania, South Africa and Uganda. South-South partnerships are actively encouraged and countries outside of this list can be included as sub-sites.
14. What is the role of the African Society of Human Genetics?
The African Society of Human Genetics (AfSHG) played an essential conceptualisation role that led to the development of H3Africa. AfSHG is a professional society of genetic researchers and health care providers across the continent and it serves as a convener for meetings to organize the genetic research community. In 2007 and 2009, AfSHG organised two meetings, in Egypt and Cameroon, to advance the idea of a project that evolved into H3Africa. AfSHG will remain engaged with the H3A community to advice and support.
15.Will the data collected by H3Africa be publically available in Internet-accessible databases for other scientists to use?
H3Africa is a project that will produce data that will be of great use to the wider research community, and as such, all of the data will be made freely available in public databases, and in accordance with all the joint funders data policies.
The speed with which the data is made public may vary from project to project, depending on the available resources. H3Africa has a Data Sharing, Access and Release policy that has been developed that describes the data sharing policy and access procedures for the research community (http://h3africa.org/consortium/documents). Data and biospecimen requests will be through application to the H3Africa Data and Biospecimen Access Committee (http://h3africa.org/consortium/documents) and data access will be via the European Genome-Phenome Archive (EGA). Data collation and transfer to the EGA will be facilitated by H3ABioNet (http://h3abionet.org), the dedicated informatics network for H3Africa.
16.Will African communities be consulted (as with the HapMap project) before individuals in the community are asked to participate in an H3Africa research project under this effort, or will only individual participants be asked to give informed consent?
Participants in individual studies will be asked to give informed consent to share samples and data. H3Africa recognises ongoing community engagement and the building of trust relationships with research participants as an essential feature of ethical biomedical and population-based genomics research involving human subjects. Community engagement can include a variety of activities, such as broad consent for sharing of samples and data, re-contact of research participants, return of results to individual participants, or other relevant topics.
The goal is to help communities understand the research aims of H3Africa and that it may have an impact on their health, but it is not expected that the consultation will be as extensive as HapMap.
17.Will biological samples – blood, DNA – be taken out of Africa?
H3Africa supports three Biorepository Programmes located in Eastern, Western, and Southern Africa. All DNA samples collected as part of an H3Africa project must be deposited in one of the H3Africa Biorepositories according to H3Africa policies (www.h3africa.org/consortium/documents) so that they can be distributed and shared for further research consistent with achieving the goals of this funding initiative.
Other biological samples may also be banked for future use. Samples may be shipped out of Africa for genomic or other ‘omic’ analysis if a particular project relies on such facilities through another, non-African partner.
18. Do the terms governing GSK funded awards differ to those funded by AESA and NIH?
GSK awardees will largely be expected to follow the principles of H3Africa relating to data sharing, collaboration and best practice in genetics research, but at all times will comply with the requirements of their particular collaboration agreement with GSK.