A5025290606- Suicide and Self-Harm Studies
- Genetic Associations and Epidemiology
- Bipolar Disorder and Treatment
- Genetic Neurodegenerative Diseases
- Tryptophan and brain disorders
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Child and Adolescent Psychosocial and Emotional Development
- Psychosomatic Disorders and Their Treatments
- Mental Health Research Topics
- Autism Spectrum Disorder Research
- Health, Environment, Cognitive Aging
- Substance Abuse Treatment and Outcomes
- Restraint-Related Deaths
- COVID-19 and Mental Health
- Cannabis and Cannabinoid Research
- Child Welfare and Adoption
- Genomics and Rare Diseases
- Child Abuse and Trauma
- Traumatic Brain Injury Research
- Healthcare professionals’ stress and burnout
- Adolescent and Pediatric Healthcare
- Ion channel regulation and function
- Genetics, Aging, and Longevity in Model Organisms
- Prenatal Substance Exposure Effects
Huntsman Cancer Institute
2021-2025
University of Utah
2017-2025
Huntsman (United States)
2020-2024
Virginia Commonwealth University
2020-2023
University of Iowa
2016-2021
University of Utah Health Care
2021
Utah State University
2008
Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are major source disability social economic burden. Both have substantial genetic etiology, partially shared distinct from that related psychiatric disorders.
Death by suicide is a highly preventable yet growing worldwide health crisis. To date, there has been lack of adequately powered genomic studies suicide, with no sizable death cohorts available for analysis. address this limitation, the authors conducted first comprehensive analysis using previously unpublished genotype data from large population-ascertained cohort.
<h3>Context</h3>The single-nucleotide polymorphism rs1344706 in the gene ZNF804a has been associated with schizophrenia and quantitative phenotypic features, including brain structure volume core symptoms of schizophrenia.<h3>Objective</h3>To evaluate associations schizophrenia.<h3>Design</h3>Case-control analysis covariance.<h3>Setting</h3>University-based research hospital.<h3>Participants</h3>Volunteer sample 335 individuals spectrum disorders (306 schizophrenia) 198 healthy...
Suicide is an urgent public health crisis that claimed over 48,000 lives in the US 2022. The importance of genetics suicide risk has been established by classical twin and family studies, confirmed with recent large genome-wide association studies (GWAS). While GWAS are beginning to reveal genetic due common variants each small effect on liability, these results explain only a fraction risk. As other complex conditions, some this unexplained likely rarer larger liability. Using whole genome...
Though suicide attempt is the most robust predictor of death, few who go on to die by (<10%), and ∼50% all deaths occur in absence evidence prior attempts. Risks this latter group are particularly poorly understood. Data from Utah Suicide Mortality Risk Study (USMRS) were used study underlying polygenic liabilities among without nonfatal suicidal thoughts or behaviors (SD-N) compared with suicidality (SD-S). We an analysis covariance design, comparing SD-N SD-S population controls similar...
Suicidality phenotypes, consisting of suicidal ideation (SI), suicide attempt (SA), and death (SD), are all heritable but present unique challenges in genome-wide association studies (GWAS) due to their individual complexity, overlap with each other related self-harm varying associations psychiatric disorders. GWAS have uncovered several loci associated suicidality phenotypes by meta-analyzing data from multiple cohorts. However, combining datasets many research groups, where group may use...
Suicidal behavior imposes a tremendous cost, with current US estimates reporting approximately 1.3 million suicide attempts and more than 40,000 deaths each year. Several recent research efforts have identified an association between suicidal the expression level of spermidine/spermine N1‐acetyltransferase 1 ( SAT1 ) gene. To date, several genetic variants been inconsistently associated altered gene and/or directly behavior. clarify role variation plays in risk, we present whole‐gene...
Recent large-scale genome-wide association studies (GWAS) have started to identify potential genetic risk loci associated with of suicide; however, a large portion suicide-associated factors affecting gene expression remain elusive. Dysregulated expression, not assessed by GWAS, may play significant role in increasing the suicide death. We performed first comprehensive genomic analysis prioritizing brain quantitative trait (eQTLs) within regulatory regions deaths from Utah Suicide Genetic...
The addition of a methyl group to, typically, cytosine-guanine dinucleotide (CpG) creates distinct DNA methylation patterns across the genome that can regulate gene expression. Aberrant CpG sites has been associated with many psychiatric disorders including bipolar disorder (BD) and suicide. Using SureSelectXT system, Methyl-Seq, we investigated status throughout in 50 BD individuals (23 subjects who died by suicide 27 from other causes) 31 nonpsychiatric controls. We identified...
Identification of genetic factors leading to increased risk suicide death is critical combat rising rates, however, only a fraction the variation influencing has been accounted for. To address this limitation, we conducted first comprehensive analysis rare in leveraging largest biobank, Utah Suicide Genetic Risk Study (USGRS). We single-variant association (minor allele frequency <1%) putatively functional single-nucleotide polymorphisms (SNPs) present on Illumina PsychArray genotyping array...
Abstract Bipolar disorder (BP) suicide death rates are 10–30 times greater than the general population, likely arising from environmental and genetic risk factors. Though suicidal behavior in BP has been investigated, studies have not addressed combined clinical factors specific to death. To address this gap, a large, harmonized cohort was assessed identify for attempt which then directed testing of underlying polygenic risks. 5901 individuals European ancestry were assessed: 353 with 2498...
ABSTRACT Nonfatal suicidality is the most robust predictor of suicide death. However, only ∼10% those who survive an attempt go on to die by suicide. Moreover, ∼50% deaths occur in absence prior known attempts, suggesting risks other than nonfatal need be identified. We studied data from 4,000 population-ascertained and 26,191 population controls improve understanding leading This study included 2,253 3,375 with evidence (SUI_SI/SB CTL_SI/SB) diagnostic codes natural language processing...
Abstract Background Standardized definitions of suicidality phenotypes, including suicidal ideation (SI), attempt (SA), and death (SD) are a critical step towards improving understanding comparison results in suicide research. The complexity contributes to heterogeneity phenotype definitions, impeding evaluation clinical genetic risk factors across studies efforts combine samples within consortia. Here, we present expert data-supported recommendations for defining control phenotypes...
Suicidal behavior has been shown to have a heritable component that is partly driven by psychiatric disorders [Brent and Mann, 2005]. However, there also an independent factor contributing the heritability of suicidal behavior. We previously conducted genome-wide association study (GWAS) bipolar suicide attempters non-attempters assess this [Willour et al., 2012]. This GWAS implicated glutamatergic neurotransmission in attempted suicide. In current study, we targeted next-generation...
Suicidal behavior is a complex and devastating phenotype with heritable component that has not been fully explained by existing common genetic variant analyses. This study represents the first large-scale DNA sequencing project designed to assess role of rare functional variation in suicidal risk. To accomplish this, whole-exome data for ∼19,000 genes were generated 387 bipolar disorder subjects history suicide attempt 631 no prior attempts. Rare variants assessed all exome as well pathways...
Abstract Suicide accounts for >800,000 deaths annually worldwide; prevention is an urgent public health issue. Identification of risk factors remains challenging due to complexity and heterogeneity. The study suicide with increased extended familial provides avenue reduce etiological heterogeneity explore traits associated genetic liability. Using extensive genealogical records, we identified high‐risk families where distant relatedness suicides implicates risk. We compared phenotypic...
Abstract Objective Suicidal behavior is heritable and a major cause of death worldwide. Two large-scale genome-wide association studies (GWAS) recently discovered cross-validated significant (GWS) loci for suicide attempt (SA). The current study leveraged the genetic cohorts from both to conduct largest GWAS meta-analysis SA date. Multi-ancestry admixture-specific meta-analyses were conducted within groups African, East Asian, European ancestry admixtures. Methods This was comprised 22...
Glutamatergic signaling is the primary excitatory neurotransmission pathway in brain, and its relationship to neuropsychiatric disorders of considerable interest. Our previous attempted suicide genome-wide association study, numerous studies investigating gene expression, genetic variation, DNA methylation have implicated aberrant glutamatergic risk. The LRRTM4 was an associated identified our with support seen primarily females. Recent evidence has also shown that partly regulated by...
FKBP5 is a critical component of the Hypothalamic-Pituitary-Adrenal (HPA) axis, system which regulates our response to stress. It forms part complex chaperones, inhibits binding cortisol and glucocorticoid receptor translocation nucleus. Variations in both HPA axis have been associated with suicidal behavior. We developed systematic, targeted sequencing approach investigate coding regulatory regions or near 476 bipolar disorder suicide attempters 473 non-attempters. Following stringent...