Utah Suicide Genetics Project
Genetic risk factors for familial suicide. Suicide is the cause of over 33,000 deaths per year in the United States (1.3% of all US fatalities) and accounts for about 2% of deaths worldwide. In particular, Rocky Mountain States have the highest age-adjusted suicide rates in the US, and Utah is consistently in the top ten. These statistics, and several unique data resources in Utah, have contributed to the development of the Utah Suicide Genetics Project. Studying the genetics of suicide is a daunting task. As opposed to genetically simple illnesses such as Huntington’s disease, suicide is very heterogeneous. Most individuals who commit suicide struggle with mental illness. However, most individuals with mental illness do not commit suicide, which suggests that additional specific risk factors, some of which may be genetic, probably exist. Suicidal behavior, and more specifically, the completion of suicide, is dependent on a multitude of genetic factors, which are interacting with unknown environmental stressors. These factors differ between individuals, and many combinations of genetic and environmental factors can lead up to the same endpoint – suicide.
Critical role of the Utah State Office of the Medical Examiner. In collaboration with the Utah State Office of the Medical Examiner, a team of University of Utah, Utah Health Department, and Intermountain Healthcare researchers are studying one of the largest DNA collections from suicide victims in the world, now over 3,500 cases. The research team first obtained ethical approvals from the University of Utah Institutional Review Board (IRB), in addition to IRBs at the Utah State Health Department and Intermountain Healthcare. Through these approvals, this DNA resource was made still more valuable by being linked to the Utah Population Database (UPDB), holding medical, demographic and genealogic information. With the help of these data elements, the research team is setting out to identify specific gene risk variants, while controlling for the influence of other factors such as psychiatric and physical disorders, hence being able to sort out the gene variants that are related to an increased risk of suicide per se.
Co-morbid conditions. The research team includes wide-ranging collaborations with scientists and research institutions. Among other factors, the joint ventures will be investigating the co-morbidity of suicide and other conditions, such as post-traumatic stress disorder, cardiovascular disorders, and opiate abuse. One of the collaborative efforts deals with the co-morbidity of suicide and asthma, two seemingly disparate conditions. This research is based on well-documented observations that asthma sufferers have a significant risk of suicidal behavior. Looking into the genetics of this co-occurrence in the large Utah data resource will be an important contribution. Understanding how genes and environment interact is one of the most important issues facing genetics research. Since the likelihood of developing a psychiatric condition is dependent on an abundance of both genetic and environmental risk factors, it is not enough to perform isolated studies of genes or environmental hazards. In yet another collaborative project, the team therefore, studies suicide victims exposed to specific environmental conditions. Suicide cases with these exposures might carry genetic factors making them more vulnerable to the particular environmental impact, increasing the risk for suicide.
Future directions: In a recently initiated project through additional IRB approval, the team is collecting skin biopsies from suicide victims, and post-mortem brain tissue with next-of-kin consent. As with the DNA, all tissue samples are linked to the database resources in the UPDB, but then are completely de-identified for subsequent research. Using brain tissue, it is possible to look for expression of the genes identified in the DNA samples. Given the heterogeneity of suicide, it is crucial to look at the right sample subset in the post-mortem tissue.
Publication titles and links to the articles for which samples and data from the OME contributed to the research are:
“Genetic risk factors in two Utah pedigrees at high risk for suicide”, Hilary Coon, lead author: http://www.ncbi.nlm.nih.gov/pubmed/24252905
“Identifying rare variants for genetic risk through a combined pedigree and phenotype approach: application to suicide and asthma”, Todd Darlington, lead author: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350517/
“Comparative analysis of suicide, accidental, and undetermined cause of death classification”, Doug Gray, lead author: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411039/
“Acute air pollution exposure and risk of suicide completion”, Amanda Bakian, lead author: http://aje.oxfordjournals.org/content/181/5/295.long
“Altitude is a risk factor for completed suicide in bipolar disorder”, Rebekah Huber, lead author: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981603/