Summary: New research links more than twenty genes to suicide risk that appears across generations in families.
Source: University of Utah
Every 11 minutes an American dies by suicide—about 132 people a day and more than 48,000 each year. For bereaved families and clinicians, understanding why remains urgent.
Family history is an important and increasingly studied factor. High-profile family tragedies such as those in Ernest Hemingway’s family, where multiple relatives died by suicide across generations, have long suggested heritable risks. Thousands of other families worldwide show similar patterns, prompting researchers to investigate genetic contributions to suicidal behavior.
Researchers at University of Utah Health’s Huntsman Mental Health Institute report a major genomic analysis of suicide death that identifies more than 20 genes potentially involved in increased suicide risk. Their study, one of the first comprehensive genome-wide analyses of suicide death, also reveals significant genetic overlap with psychiatric disorders and behaviors linked to suicide, including bipolar disorder, schizophrenia, and autism spectrum disorder.
The team emphasizes that suicide death is partially heritable and that genetic risk appears to track in families beyond effects attributable solely to shared environments. Understanding these genetic signals could improve risk prediction and inform prevention strategies.
“What is important about this study is that, using the whole genome, we have created a genetic risk score for suicide that predicts case-control status in the lab,” says Anna R. Docherty, Ph.D., lead author, quantitative geneticist at Huntsman Mental Health Institute, and assistant professor of psychiatry at University of Utah Health. “It can also help us study how genetics and environment interact to increase suicide risk. We are far from using any genetic risk score in the clinic, but this is the first step to quantifying biological risk for suicide in an individual.”
The study is published in the American Journal of Psychiatry.
Environmental factors—stress, isolation, financial hardship, childhood trauma and other life events—clearly influence suicide risk. Still, clinicians and researchers have long suspected biological contributors as well. “When I tell people that suicide risk is estimated to be 45% to 55% genetic, they look very surprised,” says Douglas Gray, M.D., co-author and professor of child psychiatry who specializes in suicide prevention. “They say, ‘No, it’s caused by losing a job, feeling helpless, or experiencing a romantic breakup.’ Well, if romantic breakup was the cause of suicide, we’d all be dead.”
Earlier work by the University of Utah team identified four gene variants linked to elevated suicide risk after detailed studies of 43 high-risk families. Those studies focused on specific regions of the genome. To broaden their search, Docherty and colleagues performed a genome-wide analysis of millions of DNA variants.
The researchers analyzed 3,413 DNA samples from the Utah Office of the Medical Examiner—the largest suicide death sample assembled to date—and compared them to DNA from more than 14,000 ancestry-matched individuals who did not die by suicide. Medical records were examined when available to evaluate diagnosed mental and physical health conditions.
Using a genome-wide association study (GWAS), the team screened millions of single-nucleotide polymorphisms (SNPs) and identified 22 genes across four chromosomes that may contribute to suicide death. By integrating the many SNPs into predictive models, the researchers also derived polygenic risk scores that predicted suicide-case status across independent datasets.
The analysis further revealed elevated genetic liability among suicide cases for traits and disorders known to increase risk: impulsivity, schizophrenia, and major depression. These findings suggest that some individuals who died by suicide carried genetic susceptibilities for psychiatric conditions that may not have been fully captured in medical records.
The authors caution that genetics is only one part of a complex causal chain. “Death by suicide typically requires a cascade of events,” Gray explains. “That cascade could include a genetic predisposition combined with untreated or undertreated mental illness, substance abuse, daily life stresses when the brain isn’t functioning well, firearm availability, and a final triggering event such as a relationship loss.”
Study limitations include the predominance of cases with Northern European ancestry and incomplete medical record data for some individuals, which may obscure psychiatric diagnoses due to care received outside the state, lack of insurance, cultural factors, or stigma. The authors plan to expand future research to larger, more diverse samples, including individuals of Mexican and Native American ancestry.
“This study and others that follow will help us better understand the constellation of risk factors associated with suicide and help reduce stigma,” Docherty says. “It may encourage families with a history of suicide to discuss risk and protective factors openly, as they would for other heritable medical conditions like high blood pressure or heart disease.”
About this genetics and mental health research news
Source: University of Utah
Contact: Doug Dollemore – University of Utah
Image: The image is in the public domain
Original Research: Closed access. “Genome-Wide Association Study of Suicide Death and Polygenic Prediction of Clinical Antecedents” by Anna R. Docherty et al., American Journal of Psychiatry
Abstract
Genome-Wide Association Study of Suicide Death and Polygenic Prediction of Clinical Antecedents
Death by suicide is a highly preventable yet growing global health crisis. Until now, adequately powered genomic studies of suicide death have been limited by small cohorts. To address this gap, the authors conducted a comprehensive genomic analysis of suicide death using previously unpublished genotype data from a large, population-ascertained cohort.