Conrad Iyegbe
Post-Doctoral Research FellowIcahn School of Medicine at Mount Sinai
Niran Okewole
Chief Consultant PsychiatristNeuropsychiatric Hospital, Aro
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, their goal is 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 GWAS participants are of European descent, a 2019 to study found, and about 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 Task Force in September, chaired by Conrad Iyegbepostdoctoral researcher in genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York City, and Niran Okewolechief consultant psychiatrist at Aro Neuropsychiatric Hospital in Abeokuta, Nigeria.
Spectrum spoke with Iyegbe and Okewole about the importance of Africa for psychiatric genomics and their plans for the working group.
This interview has been edited for length and clarity.
Spectrum: Why is more psychiatric genomics 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 for 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 to this paradigm: African genomes are replete with variants that are rare or absent in other parts of the world. They also provide higher resolution for pinpointing the precise location of important variants.
Niran Okewole: The dominant perspective on the origin of humanity is the ‘Out of Africa’ hypothesis. If that’s the case, it seems to me that there’s no way to understand how a human trait has evolved over the years, how it has survived evolutionary pressures over time, if you don’t include African populations. We cannot understand a tree if we do not understand what is happening in the roots. We cannot understand a building if we do not understand its foundations. We cannot understand human behavior if we do not have a framework that includes Africa.
Furthermore, if you think in terms of fairness and justice, if you make a scientific discovery that leads to an intervention that would be beneficial to humanity, if a large part of the human population is excluded from such an exercise, there is no justice. without equity.
S: Why can African populations be so informative in genetic research?
CI: Although people of African descent make up only about 2.5 percent of GWAS participants, they account for more than 7 percent of all disease-related discoveries made with GWAS.
According to the Out of Africa hypothesis, populations around the world can capture at most 85 percent of the genetic variation found in Africa. If we could reinvent the GWAS paradigm now based on what we have learned over the past 15 years, we probably would have started with African populations to better capture knowledge not only useful to African populations, but also to populations outside of Africa.
S: How did you get 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 conducted in psychiatry were not really exciting, but then the PGC got big enough samples to get everyone excited. I was in a session where they showed a map of all the different parts of the world where the samples came from, and Africa was just this black hole. It was clear to me at the time that this was something that needed to change.
CI: At the end of 2021, a group of young researchers, who until then had been working proactively and independently to advance a research agenda for psychiatric genomics in Africa, came together for a meeting, and we could have done it much sooner, if It wasn’t for COVID-19. Niran and I were part of that meeting, organized by Professor Karestan Koenen at Harvard, a principal investigator of the NeuroGAP-Psychosis research program in Southern and Eastern Africa. The plan to start an African task force was hatched in the context of that meeting and seemed more feasible given Karestan’s previous experience in creating the PGC task force on post-traumatic stress disorder.
S: What has the working group done so far?
NO: It is still early. So far we have focused on reaching people interested in African psychiatric genetics across the continent and the African diaspora around the world. We have scheduled monthly meetings and together we are designing an agenda for Africa’s equal immersion in the field.
One important thing we are doing is writing funding requests that will allow us to meet our schedule. We are also identifying members who are qualified to serve as liaisons for the various PGC working groups. This is a way of ensuring 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 Y NeuroGAP. We want to leverage these partnerships to empower African analysts to track wherever African data moves and support research on it, and to semi-autonomously develop and fulfill their own sites and research agendas so they don’t have to rely on collaborators. outsiders who could 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 spoken about how it would be wrong for our understanding of what it means to be African to be what is found on the land of the continent; it is also necessary to look beyond its shores. This idea of what is Africa or African is fluid, and we have come to recognize that we would be doing ourselves a disservice by not taking the diaspora into account.
CI: For people like me, who are part of the established diaspora and have never known what it is like to live in Africa, we still feel the pull of the continent and want to do what we can to help. Niran and I provide a convenient link between two key groups: Africans living in Africa and a global African diaspora that is willing to participate and want to share their skills, training and experience.
Cite this article: https://doi.org/10.53053/MCJO1377
