A genetics study in Africa is helping to destigmatize neurodevelopmental differences in children

The largest genetic study of autism spectrum disorder and other neurodevelopmental differences ever conducted in South Africa and Kenya aims to find underlying causes while helping to train young geneticists.

Growing up in Nairobi, Kenya, Patricia Kipkemoi spent years watching a young family member struggle with a neurodevelopmental disability. The family faced many challenges: finding a doctor who could pin down a diagnosis, lack of affordable education, and harsh stigma in a country where children with neurodevelopmental differences (NDDs), such as autism spectrum disorder, are often seen as stubborn or undisciplined. 

These experiences led Kipkemoi to study behavior and child development. She went abroad to do graduate work in developmental psychology, and recently returned to Kilifi, Kenya, a small, rural town on the coast, as a researcher in the NeuroDev study  the largest, most comprehensive study on the genetics of child development ever conducted in Kenya and South Africa. NeuroDev is a collaborative project between the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, the KEMRI|Wellcome Trust Research Program in Kilifi, Aga Khan University in Nairobi, Kenya, and the University of Cape Town in South Africa.

“It’s exciting that we are doing this type of work in rural Kenya,” Kipkemoi said. She is a graduate student in developmental psychology with Vrije University in Amsterdam and the KEMRI|Wellcome Trust Research Programme in Kilifi, which is a partnership between the Kenya Medical Research Institute, the Wellcome Trust, and the University of Oxford. “Much of the focus has been in urban settings, so it's great that we are reaching people who might otherwise not be involved in such studies.”

More than 5,000 participants recruited from hospitals, clinics, and schools in South Africa and Kenya will contribute to a rich genetics dataset that will help scientists in Africa and across the globe better understand the underlying genetics of neurodevelopmental differences, including intellectual disability, autism spectrum disorder, and certain learning disabilities. Most of the children enrolled in the study so far are more severely affected by these neurodevelopmental differences.

Over six years, NeuroDev researchers aim to collect and analyze DNA samples and in-depth cognitive, behavioral, and environmental assessments from children with these differences, their parents, as well as typically developing children.  

The NeuroDev team will use the data to perform genetic association studies, which will help shed light on the biological basis of neurodevelopmental differences. The researchers hope that other African scientists will use the genetic, behavioral, and environmental data to further study childhood development in an African context, and that insights from NeuroDev and future studies will one day be used to improve diagnosis and support of people with NDDs in the region. 

“This study will create a foundation for future research. We’ll learn, more comprehensively, what children with NDDs look like in African populations,” said Kirsty Donald, professor of pediatrics at the University of Cape Town and one of NeuroDev’s three principal investigators based in Africa. 

When designing the study, the NeuroDev team consulted with local communities. And as part of their work, they regularly speak with community members and healthcare workers to raise awareness about neurodevelopmental differences and their biological roots, and to help lessen the stigma that’s often associated with these conditions. 

Now in its fourth year, NeuroDev is gaining momentum in recruiting volunteers, sequencing DNA, and is already identifying new regions of the genome linked to neurodevelopmental differences. Despite shutting down for several months in 2020 due to COVID-19, operations have resumed.

NeuroDev team members in Kilifi, Kenya (left to right): Eunice Chepkemoi, Javan Nyale, Katini Mwangasha, Collins Kipkoech, and Martha Kombe. They are involved in recruiting and enrolling participants, and collecting and managing study data.

In South Africa, researchers are able to return sequencing results to some patients and their families. Donald says that for some parents, knowing that a change in a certain gene is causing their child’s NDD may offer more clarity about their child’s behavior and health status, and about the likelihood that any future children may have the same neurodevelopmental difference. 

“This is an opportunity for us to explain to families what it means to have a genetic variant linked to a neurodevelopmental difference, to give them closure around the kind of underlying cause of their child's genetic condition, and to help them think about the potential chance of recurrence,” said Donald.

NeuroDev scientists are also training early-career researchers in Kenya and South Africa like Kipkemoi to perform genetic and psychology research for years to come. As part of NeuroDev, Kipkemoi is validating culturally relevant diagnostic tools, doing behavioral analyses, and educating community members in Kilifi. She will also analyze and present NeuroDev’s findings to the academic community.

“NeuroDev will accomplish quite a lot, beyond the basic scientific question. I hope we can learn more about the genetic contributions of these conditions and expand the literature globally, but we can also help members of the team like Patricia really grow in the field,” said Amina Abubakar, Kipkemoi’s mentor and NeuroDev's Kenya-based principal investigator. Abubakar is a professor and director of the Institute for Human Development at Aga Khan University in Nairobi, Kenya, and an affiliate of the KEMRI|Wellcome Trust Research Programme. 

“I also hope the time we’re spending with parents and community members can have an impact, reduce stigma, and help children access care,” Abubakar added. 

Towards equity

The prevalence of neurodevelopmental differences in Africa is estimated to be similar to global estimates — roughly three percent — but NeuroDev researchers say it could be higher. They add that in Kenya and South Africa, children with these conditions who come into clinics are often nonspeaking, have trouble grooming independently, or have significant social challenges and need more support. Approximately 80 percent of the children enrolled in NeuroDev meet criteria for intellectual disability.

This seemingly high prevalence of severely affected children could be because the healthcare system in many parts of Africa, particularly in rural areas, is not well equipped to provide care for children with developmental differences. Often, clinicians, especially in more affordable public clinics, lack the necessary training and tools to diagnose them. As a result, more mildly affected children are less likely to receive diagnoses and care.

I also hope the time we’re spending with parents and community members can have an impact,
reduce stigma, and help children access care.
Amina Abubakar, NeuroDev principal investigator, Aga Khan University, Nairobi, Kenya 

There is also a small number of studies and scientists focused on NDDs in Africa, especially compared to the thousands of such studies in the United States and Europe. This lack of inclusion of people of African descent in research on NDDs means that they may not equally benefit from new developments in the diagnosis and support of these conditions that might come from these studies. 

“The prevalence in African nations is really poorly documented because we have very few large epidemiological studies compared to other parts of the world. It’s under-researched and undocumented,” said Abubakar. 

NeuroDev leaders say that in-depth study of the genetics of neurodevelopmental differences in Africa will be a step toward greater equity in NDD research. It will also lead to new scientific insight into the biological causes of these conditions because African populations host the largest amount of human genetic diversity in the world.

“Essentially no studies like this have been done, and our findings will be novel no matter what,” said Celia van der Merwe, NeuroDev’s research director at Broad. 

Building the team

The NeuroDev study launched in 2018 as an offshoot of NeuroGAP-Psychosis, a large, comprehensive study in four African countries on the genetic underpinnings of schizophrenia and bipolar disorder, but the two studies are designed differently. 

“Because behaviorally defined disorders of childhood are even more underdiagnosed than adult psychiatric conditions in low and middle-income countries, we don’t know very much about these conditions in many places,” said Elise Robinson, an institute member at Broad, an assistant professor in the Center for Genomic Medicine and the department of psychiatry at Massachusetts General Hospital, and a NeuroDev principal investigator. “In that context, instead of doing a genome-wide association study focused on common genetic variants — which requires an exceptionally large number of samples — it made more sense to do a smaller study that was focused on rare variants and collect detailed environmental and behavioral data.”

The NeuroDev data collection group consists of two teams: one based at the University of Cape Town and led by Donald, and the other at the KEMRI|Wellcome Trust Research Programme in Kilifi, Kenya, led by Abubakar and Charles Newton, a pediatric neurologist at KEMRI and a professor at the University of Oxford. A third site, in Nairobi, Kenya, recently opened and is headed by Abubakar.

In addition to collecting genetic data from participants, the NeuroDev team uses a set of ten assessments to study behavior, such as communication skills and social traits, and potentially relevant environmental factors, such as perinatal infection. By collecting and analyzing both genetic and environmental data from children and families, the NeuroDev team aims to begin teasing apart the genetic and contextual causes of neurodevelopmental differences in Kenyan and South African populations.

Early on, the team faced challenges in designing a protocol with culturally appropriate assessments. Since the majority of studies on NDDs have been performed in Europe and North America, assessments commonly used to diagnose children often lack relevance in Africa. For example, one method for diagnosing autism spectrum disorders — assessing the level of eye contact — is a poor measure in both Kenya and South Africa, where children are expected to avoid eye contact with adults as a sign of respect. The NeuroDev team modified and evaluated a number of diagnostic assessments for children in these areas. 

“The nuance is really important to understand. If you take so-called gold standard diagnostic tools, and you apply them without considering those different contexts, you could get different results that are not valid,” said Donald. 

The NeuroDev team consulted with members of the community in both Kilifi and Cape Town, amending the study based on feedback. They also worked closely with a multinational group of ethicists, the African Ethics Working Group (AEWG), on the complicated ethical questions raised by undertaking genomic studies on NDDs in vulnerable populations. AEWG is a collaboration between the University of Oxford and 12 African universities and is funded by the Broad’s Stanley Center for Psychiatric Research.

“This was one of the hardest projects I’ve ever worked on. At first it wasn’t clear how to proceed because a study like this hasn’t been done before,” said Dorcas Kamuya, head of the health systems and research ethics department at the KEMRI|Wellcome Trust Research Programme, an associate professor at the University of Oxford, and a member of the AEWG. “Ideally, we want to understand the nature of these conditions in order to determine what health services to provide in these regions, but we’re also working with a super vulnerable population.”

“Ensuring that they understood what was being asked, especially when the genetic literacy in these regions is quite low, was difficult,” Kamuya added. “That’s why we consulted with people from the community and collaborated closely with other institutions in the AEWG, especially University of Cape Town and University of Oxford, to address these issues carefully. We were able to discuss and learn a lot from each other.”

Designing the study

NeuroDev researchers recruit children with neurodevelopmental differences, their parents, and neurotypical children from schools, clinics, and hospitals in Kilifi, Nairobi, and Cape Town. Eligible participants learn about the study and if they provide informed consent, they then donate blood or saliva samples and take part in interviews and behavioral assessments. 

A primary goal of NeuroDev is to build and share a standalone dataset for researchers across Africa to continue studying NDDs. To help do this, the team stores blood samples from study participants at KEMRI|Wellcome Trust, Aga Khan University, and the University of Cape Town, as well as in a biobank at Rutgers University managed by the US National Institute for Mental Health (NIMH) called the NIMH Repository and Genomic Resource (NRGR). 

DNA is extracted from the blood samples and a small portion of the DNA is sent to the Broad for sequencing and genomic analysis. The genetic data are deposited at NRGR, which provides a large, open dataset of DNA, RNA, and cell lines for mental health studies. Scientists seeking to use these data or samples for their research must request access from NRGR. 

The researchers say the NeuroDev dataset could have more direct and immediate clinical implications. If parents in the study consent, pictures of their children will be submitted to the National Institutes of Health’s Atlas of Human Malformation Syndromes in Diverse Populations, which is a tool used by physicians to assess and compare distinctive facial features and other key clinical syndromic features. Distinctive facial features can assist physicians in recognizing rare genetic syndromes when genetic testing isn’t available. However, children of different ethnicities have variable facial features. A more diverse atlas is invaluable at resource-constrained facilities, where diagnostic genetic testing may not be available, said Rizqa Sulaiman-Baradien, a medical geneticist who worked with the NeuroDev team while in the University of Cape Town’s pediatrics department, and is now an assistant professor of medical genetics at the University of Manitoba in Canada.

“As a medical geneticist, the atlas is very exciting. It’s an important part of diagnosis. When I did my residency training, our academic resources largely had photos of European kids. To see diverse faces in textbooks, children from different ethnicities, that is awesome,” Sulaiman-Baradien said.

In early 2020, the NeuroDev team finished collecting and analyzing pilot genetic data from 100 children with neurodevelopmental differences and their parents. The team found 13 new genetic variants that could, at least partially, explain certain neurodevelopmental differences, such as autism spectrum disorder (ASD), between children. Six of these new variants are in single genes, meaning that a mutation in just one gene correlates with an NDD. One of these single gene variants had never been linked to ASD before. This finding adds to the roughly 100 genetic variants that have previously been linked to NDDs.

“The potential for scientific discovery is huge,” said Abubakar. “We’re really only at the beginning.”

Raising awareness

Beyond increasing scientific and clinical understanding of neurodevelopmental differences, the NeuroDev team also aims to raise awareness and destigmatize these conditions among community members. At the KEMRI|Wellcome Trust Programme, a community engagement team regularly meets with residents, including community health volunteers, who are often frontline healthcare workers in the region, to talk about the biology and genetics of these differences. NeuroDev researchers like Kipkemoi have joined these efforts. 

“Because they’re very stigmatized in our community, we talk about neurodevelopmental conditions in terms of differences in genetic instructions that determine how we behave. And people have really connected with that,” said Kipkemoi, who regularly speaks with parents about NDDs. “We see children with NDDs but they’re often hidden. It’s really powerful to be able to bring awareness to these conditions.”

The South African team is also able to tell some patients and their families what genetic variant is contributing to their neurodevelopmental difference. The researchers provide this information only to families who have provided informed consent about receiving results and only in cases where researchers are confident that the variant is strongly linked to the NDD. Donald says this information may help parents learn about how their child’s condition might progress in the future and dispel any myths about cause. They may also be able to find people in the community with similar diagnoses and find support. 

“Feedback of findings is hopefully giving people some direct benefit from participating in our study,” said Donald.

Another large part of NeuroDev is devoted to building genetics research capacity in Kenya and South Africa. The study is training researchers and clinicians on how to collect and analyze genetic and behavioral data and how to communicate with patients about genetics. NeuroDev supports and trains Kipkemoi and another graduate student, Claire Fourie, who is a graduate student at the University of Cape Town and works at the South Africa site. Kipkemoi is also supported by the Global Initiative for Neuropsychiatric Genetics Education in Research (GINGER) fellows program. Funded by the Stanley Center for Psychiatric Research at the Broad Institute and the Harvard T.H. Chan School of Public Health, GINGER fellows are early-career researchers studying genetics at African institutions and work on Stanley Center-funded projects such as NeuroGAP-Psychosis and NeuroDev. 

Kipkemoi attended weekly workshops developed and taught by local researchers, as well as virtual classes, and will be part of the next generation of researchers in the region. 

“What's happened up until now, is that often the researchers from the north have come in, done the study, and then flown out again. But with this study, my Kenyan and South African colleagues actually lead the research and are truly involved in interpreting results,” said Newton, a NeuroDev principal investigator at the Kilifi site.

Looking forward

NeuroDev activities including patient recruitment have resumed at most sites, and another batch of patient samples has been sequenced at Broad. The team is now analyzing that data and is excited to see what these results will show.

“With these cross-nation collaborations, it’s so exciting to be able to learn best practices from each other. It's been working really, really well, and we learned so much from each other,” said Abubakar.

Kipkemoi says working on the NeuroDev project has put her on the career path she has been looking for. “In the future, I’m hoping to merge clinical work with research on NDDs in Africa and help improve the lives of people in the communities around us.”


The NeuroDev study is supported by the National Institute for Mental Health, the Simons Foundation Autism Research Initiative, the National Institute of Child Health and Development, and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard.