Douglas Ruderfer, PhD, Associate Professor in Genetic Medicine, Biomedical Informatics and Psychiatry at the Vanderbilt University Medical Center, and JooEun Kang, MD, a PhD student at the Vanderbilt University Medical Center, talk about how genetics play a role in suicide attempts.
Interviews conducted by Ivanhoe Broadcast News in December 2021.
What is it that you and your colleagues are looking at in your research?
RUDERFER: We’re studying the genetics of suicide. Suicide is the 10th leading cause of death in the United States; it’s top three among young adults and adolescents. The goal of studying the genetics is to inform the underlying biology that contributes to one factor of risk for suicidal behaviors, in particular the suicide attempt.
In your research, what exactly were your findings?
RUDERFER: Most individuals who have a suicide attempt have an underlying psychiatric condition. The work that we’re looking at is trying to ease apart the genetic risks for suicide attempts, specifically versus those that contribute to psychiatric disorders. What we found is that there actually is an independent genetic risk that is contributing directly to suicide attempt and is not simply through the risk for psychiatric disorders.
KANG: Our study is the largest study looking at the genetics of suicide attempt. It’s a global collaborative effort and it had over 250 investigators looking at the genetics of suicide attempt.
What are the genetic risk factors?
RUDERFER: In our work, we found two genomic regions that contribute specifically to suicide attempt. One of them appears to be mostly driven by psychiatric disorders, the other one appears to be mostly a strong risk factor for suicide attempt and has a stronger effect for suicide attempt than for psychiatric disease. Even after you condition out psychiatric disorders, this one remains significant. Unfortunately, we can’t learn much about this particular region, as there isn’t any informative biology that we can link those particular variants to currently.
With your findings, what implications can this have?
RUDERFER: The goal of studying the genetics of suicide attempt is to find some understanding of the biology that contributes to risk for these disorders, or in this case, this outcome. The hope would be to take that information and to use it as a pathway to understand ways in which we can both reduce risk or find strategies to intervene.
Besides the genetic risk, are there other types of risk factors for suicide attempts?
RUDERFER: There are many other nongenetic risk factors for suicide attempt. We didn’t study those directly, but one of the important findings that we had from the study is that an overlap of shared genetic risk between suicide attempt and other nonpsychiatric risk factors, such as sleep disorders or smoking or risk-taking behavior, is not mediated from that underlying risk for psychiatric disorders explicitly.
What surprised you most about the findings?
RUDERFER: The most surprising finding to me was just the sheer proportion of that risk that was directly contributable to suicide attempt, which is almost about half of what we found of that genetic risk is directly affecting suicide attempt as opposed to effecting suicide attempt through psychiatric conditions.
How did you go about collecting that data to analyze for this study?
RUDERFER: This was work by an international consortium. It included over 30,000 suicide attempt cases and 500,000 controls across a dozen international sites. So many individual sites from across the world came together to provide data to allow this study to be done at large scale, and it’s the largest study that’s been done by fivefold from previous work.
With the information that you found, what are some next steps that are happening after this?
RUDERFER: The next step would be to continue this effort looking for genetic variations that contribute to suicide attempt, to expand that to larger sample sizes to allow more power to identify more genetic regions that contribute, which we hope could provide more biological understanding as to what the genetic risk is telling us about the pathways to risk for suicide attempt.
KANG: The big next step for our study is looking at the broad spectrum of suicidal behaviors that are out there, and this includes even non-suicidal self-harm, suicidal ideation and suicide attempt and suicide death. There are all these different spectrums of suicidal behavior, and we still don’t know the genetics of those. We also don’t know whether it strictly goes through progression or not.
What impact can your research have on the average viewer’s life?
RUDERFER: A key aspect to this work is that although genetic risk contributes to these outcomes, like suicidal behaviors, it is not the only contributing factor; it is one of many controlling factors, and that genetics is not destiny. Importantly, there are lots of current strategies to reduce risk for suicidal behaviors that oftentimes starts with telling someone, like a friend, a family member, or a doctor, that you are struggling.
KANG: The big takeaway from our study is that it supports the multi-pronged approach when we think about suicide, especially when we think about prevention of suicide. By looking at the genetics of suicide attempt and how it relates to mental health disorders, but also nonpsychiatric traits, I think it supports the idea that there is no one risk factor that just defines suicide attempt.
What else do you feel that people should know?
RUDERFER: The most important aspect of this study is that we can identify genetic risk as a component of that overall risk for suicidal behaviors that is not at all complete and that is independent of psychiatric conditions, which often present with suicide attempt, but is biologically correlated with other nonpsychiatric risk factors, such as sleep disorders and risk-raking behaviors, that are important to consider in absolute terms of risk.
KANG: The main finding of our study was looking at the connection of depression and suicide attempt, and this was important because we know that depression is a major risk factor for suicide attempt, and we know this because the rates of suicide are higher in individuals who have depression versus people who don’t. So, we know that there is a link, but it was unknown how genetics contributes to each of this. It was unclear whether suicide attempt is simply a sequela of having a mental diagnosis, or we should think of these as two separate entities. What we found in our study was that the genetics of suicide attempt and major depressive disorder, while highly significant and correlated, they are parts of it that are not explained by depression. We found connections with nonpsychiatric risk factors, such as smoking and sleeping disorders, that are not completely explained by depression alone.
END OF INTERVIEW
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