Researchers find over 100 new genes linked to schizophrenia. It may help doctors intervene earlier

Researchers have found more than a 100 new genes that they believe are linked to schizophrenia. And part of the reason they found them, according to Ayman Fanous, is that they looked in different places than they’ve looked before.

Fanous is chair of psychiatry at the University of Arizona College of Medicine, Phoenix and at Banner University Medicine Center in Phoenix. He was part of this study conducted at more than a dozen schools.

He spoke with The Show about the findings and what they might mean and they started with what he and his colleagues were specifically looking for.

University of Arizona

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Handout

Full conversation

AYMAN FANOUS: So, basically, if you look at the history of genetics in the last 100 plus years, even in the last, you know, 20 to 30 years, the vast majority of studies have been in European ancestry populations, say in Europe and the United States. They have really not covered populations in other parts of the world, almost at all, including in Asia, Africa, Latin America, etc.

So, one of the issues there is, can we generalize findings from European ancestry populations? And it's certainly no surprise that this kind of disparity in studying has been taking place. I mean, certainly these countries are much richer governments, etc., etc., that can spend a lot more money on science than, say, countries in Africa and Asia.

But the question again is, can we generalize the findings in European ancestry populations to other ethnic groups? And that answer — that question really has remained unanswered for quite some time now. And the reason that's an important question is, you know, the question ultimately comes down to: Are we looking at the same disorders biologically in European ancestry populations as we are in other populations?

MARK BRODIE: Well, so having done this research now, do you feel better equipped to answer the question about whether you can make that generalization?

AYMAN FANOUS: Yes, absolutely. We've taken a number of approaches in the last few years. Most importantly, we've recruited a lot more African ancestry patients. And, you know, this is a relatively recent phenomenon, I'd say going back maybe 10, 15 years. And if you look at the history of genetics in psychiatric disorders, it goes back much further than that. And one of the reasons we've been able to do that is that we've been able to recruit patients for very large what we call biobanks.

And one of the most important biobanks here in the United States is the — one that's built by the Department of Veterans Affairs. So this has allowed us to have a much larger collection of patients with all kinds of different disorders — not just schizophrenia and other psychiatric disorders, but hypertension, diabetes, etc., etc. And it's given us a much better opportunity to study pretty much all disorders in other ancestries.

So we've been able to collect to date what would be the largest study of African ancestry, as well as other ancestries as well — African ancestry patients with schizophrenia, and to try to understand sort of the genetic basis of schizophrenia in this large database, and try to see if it extends to the European ancestry population as well. In other words, are the results that we're seeing in one ethnic group, namely the African ancestry group, are they more or less the same as we're seeing in the European group? Are these disorders more or less the same biologically across these ethnic groups?

MARK BRODIE: Well, and am I right that among other things what you found is that there're more than 100 genetic links to schizophrenia that maybe you hadn't known about just based on the European studies?

AYMAN FANOUS: Yes, absolutely. I mean, if you look at the European studies in the past, they've basically given us roughly, you know, 280 genetic regions where there's probably a gene. So let's just say for simplicity's sake, they've identified 280 genes, more or less. And we've identified 100 more, including when we've included these African ancestry populations as well. So it's been very impactful in terms of getting us to a larger number of genes, getting us to a larger number of biological processes.

And one of the other important things that's happened in — in this study is that because these two populations have very different histories — one of course, as we know, the African population is — is the original human population, and so you've got a — a very diverse population in the African ancestry. And consequently, the genetics, the genome, is much more diverse in the African population. So one of the really beneficial impacts of that is that you're able to identify the location of genes in a much more precise way. In other words, let's just say you have a gene is a needle in a haystack.

When you include multiple ancestries, because of the great diversity, you get much more precision, so you get a needle in a much smaller haystack. And it allows us to more precisely identify which genes are actually involved and even, maybe even more importantly, which variations in the gene, which mutations are causing a particular protein to not function properly and therefore a particular cell not to function properly, namely a neuron. So this study has been beneficial in two important ways. Firstly, to increase the number of genes that we are confident that have an impact in schizophrenia, and secondly, to actually narrow the regions where we think those genes are.

MARK BRODIE: Does this have potential practical implications for something like, for example, diagnosing schizophrenia or treating schizophrenia or maybe even at some point trying to prevent it from showing its symptoms?

AYMAN FANOUS: Yes, I believe so. I mean, we're certainly quite a ways off from any of those possibilities, but, you know, in terms of diagnosis, now that we have a much larger number of genes that we can actually assay, we can test, you know, it would be possible, to I believe, have more predictive power to determine who is at higher risk of getting the illness.

And perhaps if we had that information, we might be able to intervene earlier, such as maybe starting people on lower doses, low doses of medication when they have early symptoms, things like that. In terms of treatment, we're now able to identify many more pathways where we might be able to have drugs that basically target these genes and might sort of intervene in the processes that lead to schizophrenia. So there might be greater drug discovery possibilities.

MARK BRODIE: It sounds like what you're saying is there are more potential ways to get at the disease now with these extra links.

AYMAN FANOUS: Absolutely. Absolutely. Of course, a lot of work needs to be done to identify, you know, ways we might be able to intervene and, you know, there's lots of different aspects of that work that will need to take place, but that definitely opens the door much wider.

MARK BRODIE: Is it possible that there are still more links out there that we just haven't found yet?

AYMAN FANOUS: Yeah, absolutely. I mean, schizophrenia, like many what we call, you know, common disorders, is very polygenic, meaning that it's not like one gene that causes the illness, as you would see in, say, cystic fibrosis. You know, it's more likely that it's like hundreds of genes, and whether it's, you know, 3 or 400 or 7 or 800, we don't really know. So that work is ongoing, but I think we're getting closer and closer to, you know, finding out.

MARK BRODIE: All right. Ayman, thank you so much for the conversation. I really appreciate it.

AYMAN FANOUS: Thank you, Mark.

MARK BRODIE: Ayman Fanous is chair of psychiatry at the University of Arizona College of Medicine, Phoenix and at Banner University Medicine Center in Phoenix.