| 1. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 2. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 3. |
- Salvatore, Jessica E., et al.
(författare)
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Parental alcohol use disorder and offspring marital outcomes
- 2019
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Ingår i: Addiction. - : Wiley. - 0965-2140. ; 114:1, s. 81-91
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We tested whether parental alcohol use disorder (AUD) predicted adult offspring's likelihood of marriage and marriage to an AUD-affected spouse; whether effects differed as a function of the sex or number of affected parents; and whether they were robust to confounders. Design: Sex-stratified Cox and logistic regression models. Setting: Sweden. Participants: A total of 1 171 070 individuals (51.40% male) born 1965–75. Measurements: Obtained from legal, medical and pharmacy registries. Predictor was parent AUD. Outcomes were marriage and spouse AUD. Adjustments included offspring birth year and AUD; and parental education, marriage, divorce, criminal behavior and drug abuse. Findings: Male and female offspring of AUD-affected parents were more likely to marry at younger ages (< 25), illustrative unadjusted hazard ratio (HR)age 20 = 1.22 (1.17, 1.28) and 1.34 (1.20, 1.39) and were less likely to marry at older ages (> 25), HRage 30 = 0.79 (0.78, 0.81) and 0.82 (0.81, 0.84). Parental AUD was associated with higher odds of having an affected spouse for males and females, odds ratio (OR) = 1.47 (1.38, 1.57) and 1.63 (1.56, 1.70). Effects were more pronounced for those with two versus one AUD-affected parent and adjustments attenuated effects negligibly. Daughters of affected mothers (versus fathers) were more likely to have AUD-affected husbands, OR = 1.68 (1.54, 1.84) versus 1.56 (1.48, 1.64), while there was no difference in sons. Conclusions: In Sweden, parental alcohol use disorder (AUD) is associated with a higher probability of marriage at younger ages, a lower probability of marriage at older ages and a higher likelihood of marriage to an affected spouse compared with no parental AUD. Most of these effects become stronger when the number of AUD-affected parents increases from one to two, and most effects hold after controlling for parents’ socio-economic status, marital history, other externalizing disorders and offspring's own AUD status. Daughters of affected mothers are more likely to have an affected spouse.
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| 4. |
- Crump, Casey, et al.
(författare)
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Comparative risk of suicide by specific substance use disorders : A national cohort study
- 2021
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Ingår i: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956. ; 144, s. 247-254
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Tidskriftsartikel (refereegranskat)abstract
- Substance use disorders (SUDs) are important risk factors for suicide, yet little is known about how suicide risks vary by specific SUDs. We examined these risks for the first time in a large general population to facilitate comparisons across SUDs. A national cohort study was conducted of all 6,947,191 adults in Sweden. SUDs (opioid, sedative/hypnotic, hallucinogen, cannabis, amphetamine, cocaine, and alcohol use disorders) were identified using inpatient, outpatient, and crime data, and suicide deaths using nationwide death data with follow-up during 2003–2016. Cox regression was used to compute hazard ratios (HRs) for suicide death while adjusting for sociodemographic factors and psychiatric, SUD, and somatic comorbidities. Co-sibling analyses assessed for confounding by unmeasured shared familial (genetic and/or environmental) factors. In 79.8 million person-years of follow-up, 15,616 (0.2%) suicide deaths were identified. All SUDs were associated with significantly increased risks, with HRs ranging from 12- to 26-fold and 2.5- to 6.4-fold before and after adjusting for covariates, respectively. After adjusting for all covariates, opioid use disorder was the strongest risk factor (HR, 6.39; 95% CI, 5.53–7.38) (P ≤ 0.002 compared with any other SUD), followed by sedative/hypnotic use disorder (4.62; 4.06–5.27) (P ≤ 0.009 compared with any other SUD except opioid or hallucinogen). Most associations persisted after controlling for shared familial factors, consistent with causal effects. In this large national cohort, all SUDs were associated with significantly increased risks of suicide death, especially opioid and sedative/hypnotic use disorders. These findings may improve risk stratification and inform interventions to prevent suicide in the highest-risk subgroups with SUDs.
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| 5. |
- Crump, Casey, et al.
(författare)
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Health care utilization prior to suicide in adults with drug use disorders
- 2021
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Ingår i: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956. ; 135, s. 230-236
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Tidskriftsartikel (refereegranskat)abstract
- Drug use disorders (DUD) are associated with psychiatric illness and increased risks of suicide. We examined health care utilization prior to suicide in adults with DUD, which may reveal opportunities to prevent suicide in this high-risk population. A national cohort study was conducted of all 6,947,191 adults in Sweden, including 166,682 (2.4%) with DUD, who were followed up for suicide during 2002–2015. A nested case-control design examined health care utilization among persons with DUD who died by suicide and 10:1 age- and sex-matched controls from the general population. In 86.7 million person-years of follow-up, 15,662 (0.2%) persons died by suicide, including 1946 (1.2%) persons with DUD. Unadjusted and adjusted relative risks of suicide associated with DUD were 11.03 (95% CI, 10.62–11.46) and 2.84 (2.68–3.00), respectively. 30.4% and 52.3% of DUD cases who died by suicide had a health care encounter within 2 weeks or 3 months before the index date, respectively, compared with 5.9% and 24.3% of controls (unadjusted prevalence ratio and difference, <2 weeks: 5.20 [95% CI, 4.76–5.67] and 24.6 percentage points [22.5–26.6]; <3 months: 2.15 [2.05–2.26] and 27.9 [25.6–30.2]). However, after adjusting for psychiatric comorbidities, these differences were much attenuated. Among DUD cases, 72.5% of last encounters within 2 weeks before suicide were in outpatient clinics, mostly for non-psychiatric diagnoses. In this large national cohort, suicide among adults with DUD was often shortly preceded by outpatient clinic encounters. Clinical encounters in these settings are important opportunities to identify suicidality and intervene accordingly in patients with DUD.
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| 6. |
- Crump, Casey, et al.
(författare)
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Healthcare utilisation prior to suicide in persons with alcohol use disorder : National cohort and nested case-control study
- 2020
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 217:6, s. 710-716
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Tidskriftsartikel (refereegranskat)abstract
- Background Alcohol use disorder (AUD) is common and associated with increased risk of suicide. Aims To examine healthcare utilisation prior to suicide in persons with AUD in a large population-based cohort, which may reveal opportunities for prevention. Method A national cohort study was conducted of 6 947 191 adults in Sweden in 2002, including 256 647 (3.7%) with AUD, with follow-up for suicide through 2015. A nested case-control design examined healthcare utilisation among people with AUD who died by suicide and 10:1 age- and gender-matched controls. Results In 86.7 million person-years of follow-up, 15 662 (0.2%) persons died by suicide, including 2601 (1.0%) with AUD. Unadjusted and adjusted relative risks for suicide associated with AUD were 8.15 (95% CI 7.86-8.46) and 2.22 (95% CI 2.11-2.34). Of the people with AUD who died by suicide, 39.7% and 75.6% had a healthcare encounter <2 weeks or <3 months before the index date respectively, compared with 6.3% and 25.4% of controls (adjusted prevalence ratio (PR) and difference (PD), <2 weeks: PR = 3.86, 95% CI 3.50-4.25, PD = 26.4, 95% CI 24.2-28.6; <3 months: PR = 2.03, 95% CI 1.94-2.12, PD = 34.9, 95% CI 32.6-37.1). AUD accounted for more healthcare encounters within 2 weeks of suicide among men than women (P = 0.01). Of last encounters, 48.1% were in primary care and 28.9% were in specialty out-patient clinics, mostly for non-psychiatric diagnoses. Conclusions Suicide among persons with AUD is often shortly preceded by healthcare encounters in primary care or specialty out-patient clinics. Encounters in these settings are important opportunities to identify active suicidality and intervene accordingly in patients with AUD.
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| 7. |
- Crump, Casey, et al.
(författare)
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Preterm birth, low fetal growth and risk of suicide in adulthood : A national cohort and co-sibling study
- 2021
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 50:5, s. 1604-1614
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adverse perinatal exposures have been associated with psychiatric disorders and suicidal behaviours later in life. However, the independent associations of gestational age at birth or fetal growth with suicide death, potential sex-specific differences, and causality of these associations are unclear. Methods: A national cohort study was conducted of all 2 440 518 singletons born in Sweden during 1973-98 who survived to age 18 years, who were followed up through 2016. Cox regression was used to compute hazard ratios (HRs) for suicide death associated with gestational age at birth or fetal growth while mutually adjusting for these factors, sociodemographic characteristics and family history of suicide. Co-sibling analyses assessed the influence of unmeasured shared familial (genetic and/or environmental) factors. Results: In 31.2 million person-years of follow-up, 4470 (0.2%) deaths by suicide were identified. Early preterm birth (22-33 weeks) was associated with an increased risk of suicide among females [adjusted hazard ratio (HR), 1.97; 95% confidence interval CI), 1.29, 3.01; P = 0.002) but not males (0.90; 0.64, 1.28; P = 0.56), compared with full-term birth (39-41 weeks). Small for gestational age was associated with a modestly increased risk of suicide among females (adjusted HR, 1.27; 95% CI, 1.08, 1.51; P = 0.005) and males (1.14; 1.03, 1.27; P = 0.02). However, these associations were attenuated and non-significant after controlling for shared familial factors. Conclusions: In this large national cohort, preterm birth in females and low fetal growth in males and females were associated with increased risks of suicide death in adulthood. However, these associations appeared to be non-causal and related to shared genetic or prenatal environmental factors within families.
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| 8. |
- Crump, Casey, et al.
(författare)
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Risks of alcohol and drug use disorders in prostate cancer survivors : a national cohort study
- 2023
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Ingår i: JNCI CANCER SPECTRUM. - : Oxford University Press (OUP). - 2515-5091. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer (PC) survivors may potentially use substances to cope with psychological distress or poorly controlled physical symptoms. Little is known, however, about the long-term risks of alcohol use disorder (AUD) or drug use disorders in men with PC.Methods: A national cohort study was conducted in Sweden of 180 189 men diagnosed with PC between 1998 and 2017 and 1 801 890 age-matched population-based control men. AUD and drug use disorders were ascertained from nationwide records through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors and prior psychiatric disorders. Subanalyses examined differences by PC treatment from 2005 to 2017.Results: Men with high-risk PC had increased risks of both AUD (adjusted HR = 1.44, 95% confidence interval [CI] = 1.33 to 1.57) and drug use disorders (adjusted HR = 1.93, 95% CI = 1.67 to 2.24). Their AUD risk was highest in the first year and was no longer significantly elevated 5 years after PC diagnosis, whereas their drug use disorders risk remained elevated 10 years after PC diagnosis (adjusted HR = 2.26, 95% CI = 1.45 to 3.52), particularly opioid use disorder (adjusted HR = 3.07, 95% CI = 1.61 to 5.84). Those treated only with androgen-deprivation therapy had the highest risks of AUD (adjusted HR = 1.91, 95% CI = 1.62 to 2.25) and drug use disorders (adjusted HR = 2.23, 95% CI = 1.70 to 2.92). Low- or intermediate-risk PC was associated with modestly increased risks of AUD (adjusted HR = 1.38, 95% CI = 1.30 to 1.46) and drug use disorders (adjusted HR = 1.19, 95% CI = 1.06 to 1.34).Conclusions: In this large cohort, men with PC had significantly increased risks of both AUD and drug use disorders, especially those with high-risk PC and treated only with androgen-deprivation therapy. PC survivors need long-term psychosocial support and timely detection and treatment of AUD and drug use disorders.
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| 9. |
- Crump, Casey, et al.
(författare)
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Risks of Depression and Suicide After Diagnosis With Heart Failure : A National Cohort Study
- 2022
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Ingår i: JACC: Heart Failure. - : Elsevier BV. - 2213-1779. ; 10:11, s. 819-827
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) has been associated with psychosocial distress, but other long-term mental health sequelae are unclear. Objectives: In this study, the authors sought to determine risks of major depression and suicide, susceptible time periods, and sex-specific differences after HF diagnosis in a large population-based cohort. Methods: A national cohort study was conducted of all 154,572 persons diagnosed with HF at ages 18-75 years during 2002-2017 in Sweden and 1,545,720 age- and sex-matched population-based control subjects who were followed up for major depression and suicide ascertained from nationwide inpatient, outpatient, and death records through 2018. Poisson regression was used to compute incidence rate ratios (IRRs) while adjusting for sociodemographic factors and comorbidities. Results: HF was associated with increased risks of major depression and death by suicide in both men and women, with highest risks in the first 3 months, then declining to modest risks at ≥12 months after HF diagnosis. Within 3 months after HF diagnosis, adjusted IRRs for new-onset major depression were 3.34 (95% CI: 3.04-3.68) in men and 2.78 (95% CI: 2.51-3.09) in women, and for suicide death were 4.47 (95% CI: 2.62-7.62) in men and 2.82 (95% CI: 1.11-7.12) in women. These risks were elevated regardless of age at HF diagnosis. HF was associated with significantly more depression cases in women (P < 0.001). Conclusions: In this large national cohort, HF was associated with substantially increased risks of depression and suicide in men and women, with highest risks occurring within 3 months after HF diagnosis. Men and women with HF need timely detection and treatment of depression and suicidality.
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| 10. |
- Dahlman, Disa, et al.
(författare)
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Socioeconomic correlates of incident and fatal opioid overdose among Swedish people with opioid use disorder
- 2021
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Ingår i: Substance Abuse: Treatment, Prevention, and Policy. - : Springer Science and Business Media LLC. - 1747-597X. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Opioid overdose (OD) and opioid OD death are major health threats to people with opioid use disorder (OUD). Socioeconomic factors are underexplored potential determinants of opioid OD. In this study, we assessed socioeconomic and other factors and their associations with incident and fatal opioid OD, in a cohort consisting of 22,079 individuals with OUD. Methods: We performed a retrospective, longitudinal study based on Swedish national register data for the period January 2005–December 2017. We used Cox proportional hazard models to investigate the risk of incident and fatal opioid OD as a function of several individual, parental and neighborhood covariates. Results: Univariate analysis showed that several covariates were associated with incident and fatal opioid OD. In the multivariate analysis, incident opioid OD was associated with educational attainment (Hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.94–0.97), having received social welfare (HR 1.31; 95% CI 1.22–1.39), and criminal conviction (HR 1.53; 95% CI 1.42–1.65). Fatal opioid OD was also associated with criminal conviction (HR 1.93; 95% CI 1.61–2.32). Conclusion: Individuals with low education and receipt of social welfare had higher risks of incident opioid OD and individuals with criminal conviction were identified as a risk group for both incident and fatal opioid OD. Our findings should raise attention among health prevention policy makers in general, and among decision-makers within the criminal justice system and social services in particular.
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