In 2007, the largest biological research project in the history of psychiatry, the Psychiatric Genomics Consortium (PGC), launched to elucidate the genetic basis of autism and other psychiatric conditions. Now, 15 years later, the effort includes more than 800 scientists from 36 countries and has conducted the largest genome-wide association studies (GWAS) of such conditions to date, involving more than 400,000 people. Ultimately, it aims to collect data on 100,000 people for each of nine sets of conditions, including autism, attention-deficit hyperactivity disorder (ADHD), depression and schizophrenia.
Despite the group’s global ambitions, its data sources offer a poor mirror of the world. More than 78 percent of participants in GWAS are of European ancestry, a 2019 study found, and roughly 72 percent of those people were recruited from just three countries — the United States, the United Kingdom and Iceland.
To help remedy this situation, the consortium launched the PGC Africa Working Group in September, chaired by Conrad Iyegbe, a postdoctoral research fellow in genetics and genomics sciences at the Icahn School of Medicine at Mount Sinai in New York City, and Niran Okewole, chief consultant psychiatrist at Neuropsychiatric Hospital, Aro in Abeokuta, Nigeria.
Spectrum spoke with Iyegbe and Okewole about the importance of Africa to psychiatric genomics, and their plans for the working group.
This interview has been edited for length and clarity.
Spectrum: Why is more psychiatric genomic research needed in Africa?
Conrad Iyegbe: GWAS have become more powerful over time due to increasing sample sizes and advancing methods. They are providing unprecedented insights into the biological mechanisms of psychiatric risk. We can derive an individual’s potential level of risk of a condition based on a polygenic risk score, which counts the number of genetic variants associated with a condition that a person has.
However, the progress made with GWAS has been heavily skewed in favor of European populations. This makes the predictive accuracy of polygenic risk scores in non-Europeans challenging.
Today, globally balanced approaches to gene discovery are needed. African populations are central in this paradigm — African genomes are teeming with variants that are either scarce or absent in other parts of the world. They also provide greater resolution to pinpoint the precise location of important variants.
Niran Okewole: The dominant perspective on the origin of mankind is the ‘Out of Africa’ hypothesis. If that is the case, it seems to me there is no way to understand how a human trait has evolved over the years, how it has survived evolutionary pressures over time, if you do not include African populations. We cannot understand a tree if we do not understand what is going on in the roots. We cannot understand a building if we do not understand its foundation. We cannot understand human behavior if we do not have a framework that includes Africa.
In addition, if you think in terms of equity and justice, if you make a scientific discovery that leads to an intervention that would be beneficial to mankind, if a large swath of the human population is excluded from such an exercise, there is no justice, no equity.
S: Why might African populations prove so informative in genetics research?
CI: Although people of African ancestry make up only about 2.5 percent of GWAS participants, they account for more than 7 percent of all disease-related discoveries made using GWAS.
Consistent with the Out of Africa hypothesis, populations around the world may at most capture 85 percent of the genetic variation that we find within Africa. If we could reinvent the GWAS paradigm now based on what we’ve learned from the past 15 years, we would probably have started with African populations to better capture knowledge not only useful for African populations, but populations outside of Africa.
S: How did you become involved in the Africa Working Group?
NO: I first became aware of the PGC itself when I won a travel grant to attend the World Congress of Psychiatric Genetics meeting in Boston in 2013. That was a landmark meeting — prior to that, GWAS done in psychiatry were not really exciting, but then the PGC got large enough samples to get everyone buzzing. I was at a session where they showed a map of all the different parts of the world where the samples were coming from, and Africa was just this black hole. It was clear to me at that time that this was something that needed to change.
CI: In late 2021, a group of junior researchers, who had up to that point been working proactively and independently to advance a research agenda for psychiatric genomics in Africa, came together for a meeting — and we might have done so much sooner, were it not for COVID-19. Niran and I were part of that meeting, which was hosted by professor Karestan Koenen at Harvard, a principal investigator of the NeuroGAP-Psychosis research program in South and East Africa. The plan to start an African working group was hatched in the context of that meeting and seemed all the more feasible given Karestan’s previous experience of setting up the PGC’s working group on post-traumatic stress disorder.
S: What has the working group done so far?
NO: It’s early days yet. So far we have focused on reaching out to individuals with an interest in African psychiatric genetics across the continent and the diaspora of Africans across the world. We have scheduled monthly meetings, and together we are fashioning an agenda for Africa’s equitable immersion in the field.
One major thing we are doing is writing applications for funding that will enable us to deliver our agenda. We are also identifying members who are qualified to act as liaisons for the various PGC working groups. This is one way to ensure that African interests are represented throughout the PGC and that the working group has up-to-date knowledge of all PGC activities.
We also want to strengthen links with initiatives that have a successful track record in Africa, such as GINGER and NeuroGAP. We want to leverage these partnerships to train African analysts to track wherever African data moves and support research of it, and to develop and fulfill their own sites and research agendas semi-autonomously so they don’t have to depend on external collaborators who might take the lion’s share of the credit.
S: Can you talk about the importance of connecting with Africans not only in Africa but also abroad?
NO: Nigeria’s only Nobel laureate, Akinwande Oluwole Soyinka, has talked about how it would be a mistake to have our understanding of what it means to be African be what is located on the continent’s land — there’s also a need to look beyond its shores. This idea of what is Africa or African is fluid, and we have come to recognize that we would do ourselves a disservice by not factoring in the diaspora.
CI: For people like me, who are part of the established diaspora and have never known what it’s like to live in Africa, we still feel the pull to the continent and want to do what we can to help. Niran and I provide a convenient link between two key constituencies — those Africans living in Africa, and a global African diaspora who are keen to be engaged and want to share their skills, training and experience.
