Summary: A genetic liability for major depression increases suicide risk across other psychiatric disorders.
Source: Mount Sinai Hospital
The largest genome-wide association study (GWAS) to date on suicide attempt reveals that genetic liability to depression increases an individual’s risk for suicide attempt regardless of the psychiatric disorder they are affected by, according to the work led by researchers at the Icahn School of Medicine at Mount Sinai and published June 5 in The American Journal of Psychiatry.
Suicide is a worldwide public health problem with more than 800,000 deaths due to suicide each year. Suicide and suicide attempts have an emotional toll on families and friends of those who died, as well as on attempt survivors. The Centers for Disease Control and Prevention report that suicide costs the US economy $51 billion per year in medical costs for individuals and families, lost income for families, and lost productivity for employers. These stark figures highlight the urgent need for improved prevention and treatment, yet progress has been hampered by the lack of reliable methods for predicting suicidality and a poor understanding of its biological etiology.
“Like many psychiatric disorders, suicide attempt is known to have a partially genetic underpinning and genetic studies can provide invaluable insights into the underlying biology,” says Niamh Mullins, PhD, Postdoctoral Fellow in Psychiatric Genomics. “Through the collective efforts of many researchers, we analyzed the genomes of suicide attempters and non-attempters across three major psychiatric disorders. Our data showed that suicide attempters with major depressive disorder, bipolar disorder or a schizophrenia diagnosis carry a greater genetic liability for major depression than non-attempters.”
Specifically, the current study compared the genomes of 6,569 suicide attempters and 17,232 non-attempters with major depressive disorder, bipolar disorder, or schizophrenia from the Psychiatric Genomics Consortium, an international collaboration for conducting large-scale genetic studies of psychiatric disorders. Samples were combined across 46 individual cohorts from Europe, the United States, and Australia. Using polygenic risk scores, which summarize an individual’s genetic liability to a disease based on the results of an independent genetic study, the research team showed that suicide attempters carry an increased genetic liability for depression, regardless of the psychiatric disorder they are affected by.
“These results indicate the existence of a shared genetic etiology between suicide attempt and major depression that is common to suicide attempt in different psychiatric disorders,” says Dr. Mullins. “Our study is the first consortium-based GWAS on suicide attempt and makes significant progress in increasing numbers by combining samples across clinical cohorts. However, further collaborative efforts to amass samples on an even larger scale will be essential to identify specific genetic variants which play a role in increasing risk of suicide attempt.”
This study provides novel insights into the genetic basis of suicide attempt. The ultimate goal of this research is to undercover the biological mechanisms underlying suicidality and develop new treatments and preventions, in order to reduce its burden on patients, families and healthcare systems.
Funding: Kings College London and many other research institutions contributed data to the study through the Psychiatric Genomics Consortium, which has received major funding from the National Institute of Mental Health and the National Institute of Drug Abuse.
Mount Sinai Hospital
Elizabeth Dowling – Mount Sinai Hospital
The image is in the public domain.
Original Research: Closed access
“GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores”. Niamh Mullins et al.
American Journal of Psychiatry. doi:10.1176/appi.ajp.2019.18080957
GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.
The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.
Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).
This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.