Abstract Background: Suicide risk among people with cancer may vary by sex and cancer site, reflecting different biological, psychosocial, and care-system pathways. We used statewide linked mortality and clinical data to examine whether cancer history and sex-specific cancer types differentially relate to pre-death suicidality and suicide mortality. Methods: We conducted a two-step study using population-level data from Utah linking suicide mortality, cancer, and electronic health records. First, we compared suicide decedents with versus without a prior cancer diagnosis (n=14,644) on suicidal ideation (SI), self-injurious behavior (SI), prior suicide attempts (SA), psychiatric and medical comorbidities. Second, we performed an age-and sex-matched case-control analysis of suicide decedents (cases; n=1,015) and living controls (n=9,173) to estimate adjusted odds of suicide death associated with any cancer history and specific cancer types, stratified by sex. Logistic regression models adjusted for prior suicidality, diagnosed mental and substance use disorders (SUD), and chronic medical morbidity. We also characterized the temporal sequencing of first-recorded encounter types (mental health, SUD, chronic medical, or cancer-related). Results: Among suicide decedents, those with any history of a cancer diagnosis had higher odds of pre-death SA (OR=1.27, 95% CI 1.09-1.49), SII (OR=1.34, 1.12-1.60), and SI (OR=1.29, 1.07-1.56) than decedents without cancer. Mental-health burden was substantially greater among female than male decedents (OR=7.90 vs 2.07). In case-control analyses, a history of any cancer was associated with lower overall odds of suicide death, but this aggregate effect masked heterogeneity by sex and cancer type. Among women, cervical cancer/dysplasia was over-represented in cases compared to controls (OR=1.53, 1.13-2.06), suggesting elevated risk in sex-specific, identity-salient cancers. Among men, prostate cancer was inversely associated with suicide death (OR=0.73, 0.59-0.91). First encounters for mental health and substance use were over-represented among cases of both sexes, while chronic-condition encounters suggest additional risk in men. Conclusions: In this study, any history of a cancer diagnosis was linked to greater pre-death suicidality but lower overall odds of suicide death, with important sex-and cancer-type specific differences. Patterns may support a dual-pathway model in which psychosocial/identity-related mechanisms may predominate among women with sex-specific cancers, whereas functional or disease-burden pathways may predominate among men with high-burden cancers. Tailored, sex-and cancer-type-specific suicide risk screening that leverages mental health and substance use encounter history may improve prevention in oncology settings. Citation Format: Brandy M. Byrwa-Hill, Eric T. Monson, Emily DiBlasi, Hilary Coon, Danli Chen, Michael J. Staley, Amanda V. Bakian. Suicide Risk in Oncology: Sex and Cancer Type Differences in a Case-Control Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1245.

Background: Suicide is a major public health concern, and short-term meteorological conditions may contribute to acute suicide risk. However, the independent and joint effects of temperature, solar radiation, and precipitation, and their modification by large-scale climate variability, remain incompletely understood. Methods: We conducted a bi-directional, time-stratified case-crossover study of 7,546 suicide deaths in Utah, USA from 2000-2016. Daily precipitation (mm), solar radiation (W/m2), and maximum temperature (◦C) were assigned to geocoded residential locations at time of death. Conditional logistic regression estimated odds ratios (ORs) per interquartile-range increases for same-day, single-day and cumulative day lags (CL0-6) exposures, adjusting for relative humidity and holidays. Effect modification by season, PM2.5, NO2, and El Niño-Southern Oscillation (ENSO) phase was evaluated. Quantile g-computation assessed joint effects of pairwise and three-way meteorological mixtures. Findings: In spring, solar radiation was positively associated with suicide at CL0-6 (OR 1·29, 95% CI 1·08-1·53). In summer, temperature showed the strongest positive association at CL0-6 (OR 1·22, 95% CI 1·10-1·35), and solar radiation was also positively associated at CL0-6 (OR 1·19, 95% CI 1·03-1·37). Joint effects were season-specific. Solar radiation-temperature mixture was positively associated with suicide in spring at CL0-6 (OR 1·01, 95% CI 1·00-1·01). Positive temperature and solar radiation associations were larger during El Niño periods, and temperature associations were amplified under higher NO2 concentrations. Interpretation: Short-term weather patterns may influence suicide risk in a seasonally specific manner. Findings suggest that large-scale climate variability and co-occurring air pollution may modify meteorological associations with suicide, with implications for climate-sensitive mental health surveillance and prevention.

Importance:Suicide is a leading cause of death in the United States with risk strongly influenced by Interpersonal trauma, contributing to treatment resistance and clinical complexity. Objective:To assess clinical and genetic factors in individuals who died from suicide, with and without interpersonal trauma exposure. Design:Individuals who died from suicide with and without trauma were compared in a retrospective case-case design. Prevalence of 19 broad clinical categories was assessed between groups. Results directed selection of 42 clinical subcategories, and 40 polygenic scores (PGS) for further assessment. Multivariable logistic regression models, adjusted for critical covariates and multiple tests, were formulated. Models were also stratified by age group (<26yo and ≥26yo), sex, and age/sex. Setting:A population-based evaluation of comorbidity and polygenic scoring in two suicide death subgroups. Participants:A total of 8 738 Utah Suicide Mortality Research Study individuals (23.9% female, average age = 42.6 yo) who died from suicide were evaluated, divided into trauma (N = 1 091) and non-trauma exposed (N = 7 647) individuals. A subset of unrelated European genotyped individuals was also assessed in PGS analyses (Trauma N = 491; Non-trauma N = 3 233). Exposures:"Trauma" is here defined as interpersonal trauma exposure, including abuse, assault, and neglect from International Classification of Disease coding. Main Outcomes and Measures:Prevalence of comorbid clinical sub/categories and PGS enrichment in trauma versus non-trauma exposed suicide deaths. Results:Overall, trauma-exposed individuals died from suicide earlier (mean age of 38.1 yo versus 43.3 yo; P <0.0001) and were disproportionately female (38% versus 21%, OR = 3.3, CI = 2.9-3.8). Prevalence of asphyxiation and overdose methods, prior suicidality, psychiatric diagnoses, and substance use (OR range = 1.3-3.7) were elevated in trauma exposed individuals who died from suicide. Genetic PGS were also elevated in trauma-exposed individuals who died from suicide for depression, bipolar disorder, cannabis use, PTSD, insomnia, and schizophrenia (OR range = 1.1-1.4) with ADHD and opioid use showing uniquely elevated PGS in trauma exposed males (OR range = 1.2-1.4). Conclusions and Relevance:Results demonstrated multiple convergent lines of age- and sex-specific evidence differentiating trauma-exposed from non-trauma exposed suicide death. Such findings suggest unique biological backgrounds and may refine identification and treatment of this high-risk group.

The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder and phobias) are highly prevalent, often onset early and cause substantial global disability. Although distinct in their clinical presentations, they probably represent differential expressions of a dysregulated threat-response system. Here, we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 out of the 58 associations replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism implicated in ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.

Suicide is an urgent public health crisis that claimed over 49,000 lives in the US in 2023. While genome-wide association studies of suicide are beginning to reveal genetic risk attributable to common variants with small effects on liability, these results explain only a fraction of the substantial proportion of risk due to genetics known to contribute to suicide mortality. As with other complex health conditions, some of this unexplained genetic risk is likely due to rarer variants with larger effects on liability. Using whole genome sequencing data from 1,054 population-ascertained suicide deaths from the Utah Suicide Mortality Research Study (USMRS) jointly processed with 1,230 controls, we investigated intragenic deletions as a class of genomic variation likely to disrupt gene function. To minimize false positives, deletions were limited to those found in large publicly available control datasets (1000 Genomes, GnomAD, and Centers for Common Disease Genomics) and where replication of deletions occurred across two cohorts within the USMRS suicides. Deletions meeting these filters were manually validated. Eleven deletions had at least 2-fold increase in frequency in suicide deaths vs. controls (range 2.28 to 4.46). Implicated genes were associated with mental health conditions (MPST, IL4R, CDH13), epilepsy (CLCA4), intellectual disability (ZNF44), neuronal function (OSBPL2), metabolic function (FBOX36), lipid metabolism (TM9SF3), immune functions (PIPOX, IL4R), and Alzheimer's disease (ZHX3, LMNTD1). Pending replication, these results may help prioritize biological pathways for future functional studies with the goal of increasing our understanding of risk mechanisms leading to suicide mortality.

BACKGROUND:Individual components of the ambient environment, such as temperature and air pollution, exist as part of a complex mixture and have been associated with suicide; however, their interactive effects remain poorly understood. This study examined the independent and interactive effects of wet bulb globe temperature (WBGT), nitrogen dioxide (NO2), and fine particulate matter (PM2.5) on suicide mortality. METHODS:We identified 7,551 suicide cases in Utah, USA, from 2000 to 2016 and assigned exposure to daily maximum WBGT (sourced from the European Center for Medium-Range Weather Forecasts) and PM2.5 and NO2 concentrations (sourced from a national spatiotemporal ensemble model) using decedent's residential address at the time of death. A case-crossover design with conditional logistic regression was used to estimate the independent and interactive effects of WBGTmax, PM2.5, and NO2 on suicide. For exposure windows, we considered single days preceding suicide (lag 0 to 6) and their averages across preceding days (lag 0-1, 0-3, and 0-6). Analyses were stratified by season. RESULTS:We identified a significant association between WBGTmax and suicide across all seasons (odds ratio [OR] = 1.05, 95% confidence interval [CI]: 1.01, 1.10; per 5 °C increase on lag 0-3 days). The associations were stronger in the warm season (March 22 to September 21), with ORs and 95% CIs ranging from 1.08 (1.02, 1.15) to 1.20 (1.10, 1.30) per 5 °C increase depending on the lag periods. We observed synergistic interactions between WBGTmax and PM2.5 and NO2 in the warm season, associated with higher odds of suicide. The associations of WBGTmax with suicide were most pronounced at high NO2 levels. CONCLUSIONS:We found evidence of synergistic interactions between WBGTmax and PM2.5 and NO2 on suicide in the warm season, emphasizing the need for considering the combined effects of heat stress and air pollution in suicide prevention strategies.

Chronic pain represents heritable conditions linked to suicide death. It has been suggested that a shared genetic predisposition may contribute to this relationship, but there has not yet been a comprehensive assessment of genetic and clinical overlaps of different types of chronic pain with suicide death. Here, we integrated whole-genome sequencing and electronic health records from 986 unrelated individuals of European ancestry who died by suicide in the Utah Suicide Mortality Research Study and 415 ancestrally-matched population controls selected for absence of disease. Polygenic scores (PGSs) for seven distinct types of chronic pain were calculated and tested in the suicide cohort. We observed significant positive associations of PGSs for multisite chronic pain (PGSMCP) and chronic widespread pain (PGSCWP) with suicide mortality. Sex-stratified analyses showed elevations in both males and females. Pain diagnosis-stratified analyses revealed associations with suicide death regardless of chronic pain diagnoses. Follow-up tests of PGSs for more specific pain conditions showed additional associations with suicide death for: 1) monoarticular arthritis, 2) back pain, and 3) chronic inflammatory demyelinating polyneuropathy across all suicide death individuals, and 4) irritable bowel syndrome within males only. In a multiple logistic regression test of all chronic pain PGSs associating suicide death status, four types of pain remained uniquely associated with suicide death, highlighting distinct subgroups within suicide death: some attributed to MCP and CWP, and others associated with monoarticular arthritis or chronic inflammatory demyelinating polyneuropathy. This cohort study reports associations between suicide death and PGSs from various pain conditions, regardless of sex or chronic pain diagnosis, suggesting that combining genetic and clinical risk factors may better identify genetic overlap, causal directions, and/or specific gene pathways.

Alzheimer’s disease (AD) presents a significant public health problem and major cause of dementia. Not only genetic but epigenetic factors contribute to complex and heterogeneous molecular mechanisms underlying AD risk; in particular, single nucleotide polymorphisms (SNPs) and DNA methylation can lead to dysregulation of gene expression in the AD brain. Each of these regulators has been independently studied well in AD progression, however, their interactive roles, particularly when they are located differently, still remains unclear. Here, we aimed to explore the interplay between SNPs and DNA methylation in regulating transcript expression levels in the AD brain through an integrative analysis of whole-genome sequencing, RNA-seq, and methylation data measured from the dorsolateral prefrontal cortex. We identified 179 SNP-methylation combination pairs that showed statistically significant interactions associated with the expression of 67 transcripts (63 unique genes), enriched in functional pathways, including immune-related and post-synaptic assembly pathways. Particularly, a number of HLA family genes (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB5, HLA-DPA1, HLA-K, HLA-DQB1, and HLA-DMA) were observed as having expression changes associated with the interplay. Our findings especially implicate immune-related pathways as targets of these regulatory interactions. SNP-methylation interactions may thus contribute to the molecular complexity underlying immune-related pathogenies in AD patients. Our study provides a new molecular knowledge in the context of the interplay between genetic and epigenetic regulations, in that it concerns transcript expression status in AD.

Suicide risk and health disparities intersect across both sex and cancer type through a combination of biological, psychosocial, and health-system factors. Sex-specific malignancies (e.g., breast and cervical, uterine cancer in women; prostate and testicular cancer in men) may compound psychosocial challenges, body-image disturbance, identity shifts, and social isolation, thereby deepening inequities in mental health outcomes. This study evaluates disparities in suicidal ideation (SI), self-harm (SH), and suicide attempts (SA) among decedents with and without prior cancer, disaggregating by sex and by cancer type to uncover differential vulnerability. State-level data on 14,644 suicide decedents, ascertained by the Utah Office of the Medical Examiner, were analyzed using contingency analyses and Fisher’s exact tests. Suicidality was operationalized across three domains: SI, SH, and SA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to compare suicidality between decedents with and without cancer. Analyses were stratified by sex and by cancer type (sex-specific vs. non-sex-specific): sex-specific cancers included breast, cervical, and uterine cancers in women, and prostate and testicular cancers in men; non-sex-specific cancers comprised all other malignancies not involving reproductive organs. Overall, cancer history was linked to markedly higher suicidality, disproportionately so in women (OR=7.90; 95% CI 4.90–12.73) versus men (OR=2.07; 95% CI 1.48–2.89). Among women with sex-specific cancers, 89% exhibited some form of suicidality. SI (OR=3.01; 95% CI 2.17–4.17), SA (OR=4.75; 95% CI 3.52–6.41), and SH (OR=6.05; 95% CI 4.49–8.15), compared to 51% of cancer-free decedents. In contrast, men with non-sex-specific cancers (notably lung and gastrointestinal) showed elevated SI (OR=1.50; 95% CI 1.19–1.88) and SA (OR=1.31; 95% CI 1.08–1.59), but no increase in SH. Men with prostate or testicular cancer did not differ from non-cancer decedents. These findings reveal pronounced sex and cancer-type specific disparities in suicidality among decedents with a prior cancer diagnosis. Women who experienced sex-specific cancers had a substantially higher mental health burden across all suicidality domains, underscoring an urgent need for targeted mental-health interventions in this group. In men, elevated risk was confined to non-sex-specific cancers such as colon and other cancers characterized by high symptom burden and poor prognosis, suggesting distinct functional and existential drivers. Addressing these disparities necessitates sex and cancer specific tailored mental health and suicide prevention strategies within oncology care pathways, to mitigate inequities as cancer survivorship continues to improve. Brandy M. Byrwa-Hill, Eric T. Monson, Emily DiBlasi, Hilary Coon, Danli Chen, Michael Staley, Amanda V. Bakian. Health disparities by sex and cancer type among suicide decedents [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C091.

Background:Suicidality, including suicidal ideation (SI), attempt (SA), and death (SD), represents complex and partially overlapping phenotypes. This complexity contributes to study population heterogeneity in suicidality research, impeding replication efforts and data consolidation by research consortia. The standardization of suicidality definitions would help but has been insufficiently addressed in existing literature. Here, the Suicide Workgroup of the Psychiatric Genomics Consortium (PGC) provides International Classification of Disease (ICD) definitions, a critical real-world data source, for SA and SI. Methods:The PGC Suicide Workgroup used published definitions coupled with expert consensus to develop ICD lists to serve as suicidality phenotype definitions. One SI and two SA lists were produced and evaluated for performance against patient screening responses in two independent cohorts (N = 9,151 and 12,621) with differing ascertainment strategies. Outcomes:ICD list suicidality definitions were produced. Evaluation of generated ICD lists versus patient responses across two cohorts demonstrated varied sensitivity (15·4% to 71·1%), specificity (67·6% to 96·3%), and positive predictive values (0·57-0·92). SI ICD code performance also varied in sensitivity (29·4%-86·1%), specificity (64·2% to 90·6%), and positive predictive values (0·67 to 0·98). Interpretation:Guidelines were developed to provide more consistent and comparable suicidality definitions. However, real-world application of ICD codes leads to a wide range of performance, dependent on cohort characteristics, that will need to be carefully considered in implementation. Future efforts would benefit from consistent training in use of ICD codes between sites to improve generalizability, and should include validation in diverse populations. Funding:This work was funded by NIMH R01MH132733 (Mullins), R01MH132733 (Ruderfer), R01MH123619 (Docherty), R01MH123489 (Coon), R01MH124839 (PGC4), R01MH118233 and MH117599 (Smoller), Brain and Behavior Research Foundation No. 31248 (Monson), the Huntsman Mental Health Institute, National Science Foundation Graduate Research Fellowship Program Grant #1842169, and by grant # I01BX005881 and #IK6BX006523 (Kimbrel) from the Department of Veterans Affairs.

Suicidality phenotypes, consisting of suicidal ideation (SI), suicide attempt (SA), and suicide death (SD), are all heritable but present unique challenges in genome-wide association studies (GWAS) due to their individual complexity, overlap with each other and with related self-harm phenotypes, and varying associations with psychiatric disorders. GWAS have uncovered several loci associated with suicidality phenotypes by meta-analyzing data from multiple cohorts. However, combining datasets from many research groups, where each group may use different study designs, phenotyping instruments, and definitions of suicidality phenotypes, presents challenges. Heterogeneity resulting from these differences can limit genetic discovery; harmonizing phenotype definitions to ensure consistency will greatly improve results. Here, we describe a standardized phenotyping protocol that draws on the expertise of a subgroup of clinicians, researchers, and experts from the Psychiatric Genomics Consortium Suicide Working Group to propose consensus definitions for SI, SA, and SD for genetic studies.

INTRODUCTION:Suicidality, including suicidal ideation (SI), attempt (SA), and death (SD), represents complex and partially overlapping phenotypes that are moderately heritable. Suicidality definition heterogeneity impedes data replication and consolidation efforts by research consortia needed to address the sample size requirements of genetic research. The standardization of suicidality definitions would improve comparability of data across groups but has been insufficiently addressed in existing literature. Here, the Suicide Workgroup of the Psychiatric Genomics Consortium (PGC) provides International Classification of Disease (ICD) definitions and validation in real-world data for SA and SI. METHODS:The PGC Suicide Workgroup used published definitions coupled with expert consensus to develop ICD lists to serve as suicidality phenotype definitions. One SI and two SA lists were produced and evaluated for performance, including via sex stratification, against patient screening responses in multiple independent cohorts (total N = 21,772) with differing ascertainment strategies. RESULTS:ICD code lists for suicidality component definitions were produced. SA ICD lists versus patient responses showed sensitivity of 15.4 % to 71.1 %, specificity of 67.6 % to 96.3 %, and positive predictive values of 0.57-0.92. SI ICD code performance versus patient report also varied in sensitivity (29.4 %-86.1 %), specificity (64.2 % to 90.6 %), and positive predictive values (0.67 to 0.98). CONCLUSIONS:Lists of applicable ICD codes for SI and SA were developed that complied with C-SSRS definitions. Real-world application of ICD codes can vary substantially, perhaps dependent on clinician training and on cohort characteristics. Consistent training in use of ICD codes between sites may improve comparability of data sets.

Stillbirth is a devastating adverse pregnancy outcome affecting 2 million pregnancies worldwide. Although an etiology may be found in some stillbirths, one-third remain unexplained. Stillbirth clusters in families and few underlying inherited genes associated with stillbirth are known. Well-characterized family-based studies may aid in identifying genetic contributors to unexplained stillbirth. Using the Utah Population Database, we defined pedigrees with high familial risk of stillbirth. Comprehensive phenotyping with review of primary medical records was conducted to identify stillbirth cases without identifiable causes. We generated whole-genome sequencing in seven stillborn placentas from three pedigrees. We performed shared genomic segments analysis to identify evidence for segregating haplotypes shared by the stillbirths to provide evidence for inherited risk. A region at 15q26.3 was identified in two independent pedigrees with genome-wide significance in both (a 1.2 Mb segment shared by two stillbirths in pedigree A, and a 1.8 Mb segment shared by two stillbirths in pedigree B). Four other regions reached genome-wide significance in single pedigrees at 16p13.13-p13.12, 9p13.3-p13.1, and 6p22.2-p22.1 (shared by the same two stillbirths in pedigree B), and a 0.8 Mb segment at 14q.32.2 shared by three stillbirths in pedigree C. The identified regions are implicated in in utero and postnatal development, pregnancy loss, and infertility. We identified evidence for inherited risk loci in stillbirth placental genes that are implicated in in utero and postnatal development, pregnancy loss, and infertility. Identification of inherited genes in stillbirth risk may provide therapeutic targets for prevention and treatment to improve pregnancy outcomes.

Nonfatal suicidal behavior is the most robust predictor of suicide death. However, only ∼10 % of those who survive an attempt go on to die by suicide. Moreover, ∼50 % of suicide deaths occur in the absence of prior known attempts, suggesting risks other than nonfatal suicide attempt need to be identified to help prevent suicide mortality. We studied data from 4,000 population-ascertained suicide deaths and 26,191 population controls to improve understanding of suicide deaths without prior nonfatal attempts. This study included 2,253 suicide deaths and 3,375 controls with evidence of nonfatal suicidal ideation or behaviors (SUI_SI/SB and CTL_SI/SB) from diagnostic codes and natural language processing of electronic health records notes. Characteristics of these groups were compared to 1,669 suicides with no prior nonfatal SI/SB (SUI_None) and 22,816 controls with no lifetime suicidality (CTL_None). The SUI_None and CTL_None groups had fewer overall diagnoses and were older than SUI_SI/SB and CTL_SI/SB. Mental health diagnoses were far less common in both the SUI_None and CTL_None groups; mental health problems were far less associated with suicide death than with presence of SI/SB. Physical health diagnoses were conversely more often associated with risk of suicide death than with presence of SI/SB. Pending replication, results indicate highly significant clinical differences among suicide deaths with versus without prior nonfatal SI/SB, and suggest that, for a substantial number of individuals at risk for suicide mortality, history of SI/SB does not serve as an effective clinical marker of risk.

IMPORTANCE:Transgender and gender-diverse (TGD) individuals are at risk for discrimination and inequities across legal, social, and medical contexts. Population-level resources have rarely been used for TGD health research and, therefore, data is lacking about prevalences of a wide range of clinical conditions among TGD populations. OBJECTIVE:To leverage the Utah Population Database's demographic, vital, and health records and examine population-level diagnostic prevalences in TGD individuals and an age-matched general cohort. PARTICIPANTS:6,664 TGD individuals were identified using ICD codes for gender incongruence between 1995 and 2021; 64,124 age-matched individuals comprised the control cohort. DESIGN:Using Phecodes to collapse ICD codes, this study examined differences in the prevalence of medical, mental health, and neurodevelopmental clinical phenotypes in TGD and control cohorts using modified Poisson regression models. SETTING:Affiliated healthcare systems within the state of Utah. MAIN OUTCOME AND MEASURE:We evaluated adjusted prevalence ratios of identified Phecodes. RESULTS:The TGD cohort showed broadly higher documented prevalences of medical, mental health, and neurodevelopmental conditions compared to controls. Medical diagnoses more common in the TGD cohort included sleep disorders and chronic pain. Disparities in diagnoses such as "other endocrine disorders" and "need for hormone replacement therapy" likely reflect gender-affirming treatments. Mental health conditions including mood, depression, anxiety, and personality disorders were significantly more prevalent in the TGD cohort. CONCLUSIONS AND RELEVANCE:This study highlights diagnostic disparities for TGD individuals across multiple clinical categories. Our findings may be driven by: 1) discrimination and over-medicalization of TGD individuals, 2) differences in accessing and interacting with the healthcare system, and 3) variation in the true incidence of medical and mental health outcomes in the TGD vs control cohorts.

Introduction: We are in the midst of an opioid epidemic. In the USA, more than a third of the country knows someone who has died from an opioid overdose. Prescription opioids (e.g., oxycodone, hydrocodone, and fentanyl) are commonly used and misused, and it has been estimated that approximately 8–12% of individuals who misuse opioids will subsequently develop an opioid use disorder (OUD). While emphasis has been placed on understanding OUD and the associated adverse effects, there remains a critical gap in systematically characterizing the multifactorial pathways (e.g., behavioral, clinical, genetic, and socio-demographic characteristics) that contribute to the transition from initial use to misuse to OUD. Methods: To address this gap, we introduce the Prescription Opioid Medication Survey (POMS), an online 120-item assessment that compiles multiple validated and standardized instruments. POMS is intended for individuals with any lifetime prescription opioid use. POMS captures various aspects of prescription opioid use including data on opioid use patterns, subjective effects (e.g., euphoria, nausea), problematic use, withdrawal, OUD, overdose, treatment history, and remission. It also addresses comorbid risk factors such as surgical history, chronic pain, other substance use disorders (SUD; e.g., nicotine, alcohol, cannabis, stimulants), other addictive behaviors (i.e., gambling, sexual behaviors, and gaming), and family history of SUD and other addictive behaviors. Mental health assessments, including screening for depression and anxiety, self-reports of eight psychiatric disorders (anxiety, depression, bipolar, schizophrenia, attention-deficit/hyperactivity disorder, post-traumatic stress disorder, obsessive-compulsive disorder, eating disorders), and related mental health conditions (e.g., loneliness, suicide, trauma) are included, along with data on personality traits (e.g., risk-taking, delay discounting, wisdom) and socio-demographic factors. POMS is intended to be administered in clinical settings and large population-based cohorts, facilitating data collection that can enable discoveries to inform better prevention and intervention strategies for OUD. Conclusion: POMS offers a comprehensive tool for systematically capturing the multifactorial risk factors associated with opioid misuse and OUD, providing insights that can inform prevention and intervention strategies.

Importance:Though suicide attempt is the most robust predictor of suicide death, few who attempt go on to die by suicide (<10%), and ∼50% of all suicide deaths occur in the absence of evidence of prior attempts. Risks in this latter group are particularly poorly understood. Objective:Data from the Utah Suicide Mortality Risk Study (USMRS) were used to study underlying polygenic liabilities among suicide deaths without evidence of prior nonfatal suicidal thoughts or behaviors (SD-N) compared to suicide deaths with prior nonfatal suicidality (SD-S). Design:We used an analysis of covariance design, comparing SD-N to SD-S and to population controls with similar genetic ancestry from the United Kingdom. Setting:We selected 12 source studies to generate descriptive quantitative polygenic scores (PGS) reflecting neuropsychiatric conditions. Analysis of covariance was used to evaluate suicide mortality subsets and controls adjusted for sex, age, and genetic ancestry effects. Participants:Suicide deaths were population-ascertained through a 25-year collaboration with the Utah State Office of the Medical Examiner. Evidence of suicidality was determined from diagnoses and clinical notes, yielding 1,364 SD-N and 1,467 SD-S deaths, compared to 20,368 controls. Main Outcomes:The tested PGS spanned 12 psychiatric, neurodevelopmental, and neurodegenerative conditions. Results:SD-N were significantly more male (82.33% vs. 67.76%) and older at death (47.26 years vs. 41.36 years) than SD-S. Controls were significantly less male than both suicide subsets (43.71%). Genetic ancestry was similar across suicide subsets and controls (% European: 96.77%, 96.81%, and 97.38%). Comparing SD-N to SD-S revealed significantly lower PGS in SD-N for: MDD (p=0.0015), neuroticism (p=0.0016), anxiety (p=0.0048), Alzheimer's (p=0.011), depressed affect (p=0.015), schizophrenia (p=0.020), PTSD (p=0.023), and bipolar disorder (p=0.028). This attenuation in SD-N was particularly pronounced for depressed affect, neuroticism, and Alzheimer's, where PGS were not different from controls. Sex-specific analyses suggested attenuation of PGS in SD-N was driven by males for MDD, anxiety, and PTSD, and by females for bipolar disorder, neuroticism, and Alzheimer's. Conclusions and Relevance:SD-N have significantly different genetic liabilities from SD-S, particularly regarding neuropsychiatric conditions. Results have far-reaching implications both for future research and for preventions for those at highest risk of mortality. KEY POINTS: Question:What are underlying genetic liabilities related to neuropsychiatric conditions in the roughly half of suicide deaths with no evidence of prior nonfatal suicidal thoughts or behaviors (SD-N), a group that has not previously been accessible for study? Findings:These suicide deaths with no prior nonfatal suicidality showed significantly attenuated underlying polygenic liabilities associated with mental health traditionally thought to be core features of suicide mortality risk, and justifies additional studies of underlying risks associated with non-psychiatric conditions and behaviors. Meaning:These differences in underlying liabilities between suicide deaths with and without prior suicidality suggest departure from the traditional mental health risks that have been the focus of suicide risk discovery, and impel new directions for future research and prevention efforts.

Autistic individuals are disproportionately likely to experience suicidal thoughts, feelings, and actions. Addressing suicidality is also a high priority of autistic community members. The goal of this study was to understand broad influences on suicidality and suicide-prevention needs for the autistic community. Using a community-based participatory research approach, we conducted a reflective thematic analysis of qualitative interviews with 16 autistic adults, 8 family members, and 14 mental health providers. Themes summarizing influences on suicidality and suicide-prevention needs centered on three broad thematic concepts: (1) Pervasive negative societal attitudes and social experiences have a lasting impact on autistic people's feelings of worth; (2) negative experiences and stressors add strain, making life feel overwhelming and hopeless; and (3) difficulty regulating and managing emotions can increase the likelihood of suicidal feelings and actions. Participants provided autism-specific recommendations to incorporate into suicide prevention. The findings emphasize the need for multifaceted suicide-prevention efforts supporting autistic people through improved societal treatment, community-level supports, and individually tailored services.Lay Abstract Autistic people experience suicidal thoughts, feelings, and actions more often than non-autistic people. Autistic community members say this is an important research topic. The goal of this study was to understand broadly what kinds of things might lead autistic people to feel suicidal. We also wanted to know what is needed for suicide prevention for the autistic community. The research team for this study included autistic community partners using an approach called community-based participatory research. The study team did interviews with 16 autistic adults, 8 family members, and 14 mental health providers. The results show that different types of experiences can lead to suicidality. One influence is the negative treatment of autistic people. Negative experiences, challenges, and stressors can also make life feel overwhelming for autistic people. Finally, difficult emotions can be hard to manage. There are many things that participants thought would help autistic people feel less suicidal. The study shows that autistic people need to be treated better and need more community supports to help prevent suicidal feelings. They need individualized services to help manage their emotions.