Esben Agerbo, DrMedSc, on Polygenic Risk Scores, When Used With Other Risk Factors, May Help Predict MDD

The polygenic risk score (PRS) for depression may help identify major depressive disorder when considered along with other risk factors for depression, researchers recently reported in JAMA Psychiatry.

“Incorporating the depression PRS with other risk factors should improve risk prediction in the general population, especially as genome-wide association study sample sizes increase,” the study team concluded.

In this video, lead author Esben Agerbo, DrMedSc, explains the reasons for the research, the significance of the findings, and expanding his research to include other mental health disorders.

Esben Agerbo, DrMedSc, MSc, is Head of Research and Professor, National Centre for Register-based Research, Centre for Integrated Register-based Research, Department of Economics and Business Economics, School of Business and Social Sciences, Aarhus University, Denmark. His scientific focus is on the epidemiological, environmental, and genetic underpinnings of mental health disorders, and recently entered a field described as the register-based social science genetics of mental health disorders. He is the co-author of 213 peer-reviewed publications.  

Additional Resource:

Agerbo E, Trabjerg BB, Børglum AD, et al. Risk of early-onset depression associated with polygenic liability, parental psychiatric history, and socioeconomic status. JAMA Psychiatry. 2021 January 13;[Epub ahead of print]. 


Q: What led you and your colleagues to conduct this research?

A: The background for this research was that we hadn't seen any studies that looked at the genetic liability for depression, together with other risk factors for depression, and especially, we hadn't seen any studies, estimating the absolute risk. What's the risk in the future of being diagnosed with severe depression?

Q: How was the study conducted?

A: The main method was the Danish National Register, where all cases of depression, all cases that are hospitalized, are recorded. Then we have this what we call the iPSYCH sign, which include all cases with depression in Denmark, together with a random sample of people in Denmark. All these individuals, we had access to genomic data at birth.

Q: What were your key findings?

A: The key significant finding is that both genetic—here, it's polygenic risk factors—and ordinary risk factors, such as family history for depression, are important in depression, but they do not interact. They actually act together. That's the most important finding.

Of course, family history is a good clinical question to ask, but there might also be misrecording in that, or people might not remember or know. The good thing about a genetic measure is that it applies to everybody. In that sense, they are very good alternatives, or, at least, they're very good at putting together the story. That's the main finding.

Q: Did you have any surprising or unexpected outcomes?

A: To me, personally, it was quite surprising how big the actual risk actually was. In this sample, with this definition of schizophrenia, around 15 percent of women get a diagnosis of depression throughout life. Here, we could actually predict up to 35, 40 percent before age 30. And I think that was quite surprising.

Q: Are there any clinical applications of your findings?

A: Now that genotyping is getting much cheaper, having polygenic risk, or what it is, it can be quite important in the future. Now, here, remember that this is not clinical. This is something you could think about in the population.

This study generalizes to people in the population. This is kind of asking, if you take a random sample of people at age 10, how many of them will develop, will be diagnosed with depression in the future? In that sense, that's the most important. It's not about people who show up in clinics. It's something that applies to the population.

Q: Are you doing any related research?

A: I'm doing other studies in other fields within psychiatry, in autism, and ADHD, and other severe mental disorders, where we do the same kind of thing. We ask how much can we actually predict by putting together genetic factors with environmental, or with other factors that are easily question asked factors.

That is the direction our research is taking, to putting these things together and asking questions about psychiatry in the general population.

Q: Is there anything else you would like to add?

A: Maybe, I should say, if you hypothetically somehow could take women who are at the highest risk and put them into the category of those who had the lowest risk. I don't know how to do that, and I'm not sure anybody will do that. If you somehow could mitigate the risk in the sense. You only needed 5 women to prevent 1 case of depression. That's quite interesting.