| 1. |
- Baker, Jessica H., et al.
(författare)
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Illicit Drug Use, Cigarette Smoking, and Eating Disorder Symptoms : Associations in an Adolescent Twin Sample
- 2018
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Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation. - 1937-1888 .- 1938-4114. ; 79:5, s. 720-724
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Twin studies have shown that genetic factors in part explain the established relation between alcohol use (i.e., problematic use or abuse/dependence) and eating disorder symptoms in adolescent and adult females. However, studies have yet to elucidate if there are similar shared genetic factors between other aspects of substance involvement, such as illicit drug use and repeated cigarette smoking.Method: For those sex-specific phenotypic correlations above our threshold of.20, we used a behavioral genetic design to examine potential shared genetic overlap between self-reported lifetime illicit drug use and repeated cigarette smoking and the eating disorder symptoms of drive for thinness (DT), bulimia (BU), and body dissatisfaction (BD), as assessed with the Eating Disorder Inventory-II in 16- to 17-year-old female and male twin pairs.Results: Only phenotypic correlations with illicit drug use met our threshold for twin modeling. Small to moderate genetic correlations were observed between illicit drug use and BU in both girls and boys and between illicit drug use and in girls.Conclusions: Similar etiological factors are at play in the overlap between illicit drug use and certain eating disorder symptoms in girls and boys during adolescence, such that genetic factors are important for covariance. Specifically, illicit drug use was associated with bulimia nervosa symptoms in girls and boys, which parallels previous substance use research finding a genetic overlap between alcohol use and bulimia nervosa symptoms. Future research should prospectively examine developmental trajectories to further understand the etiological overlap between substance involvement and eating disorder symptoms.
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| 2. |
- 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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| 3. |
- Edwards, Alexis C., et al.
(författare)
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Genetic differences between suicide deaths and deaths of undetermined intent
- 2023
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Ingår i: Suicide and Life-Threatening Behavior. - : Wiley. - 0363-0234 .- 1943-278X. ; 53:1, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Few, if any, prior studies have considered whether undetermined intent (UDI) deaths and suicide deaths differ with respect to genetic liability for suicidal behavior or psychopathology. Methods: The authors used Swedish national registry data to identify suicide deaths (N = 31,835) and UDI deaths (N = 10,623); sociodemographic covariates; and registrations for psychopathology. Family genetic risk scores (FGRS) were derived for each form of psychopathology. The authors used LASSO models to assess genetic and phenotypic differences across outcomes. Results: In the multivariate LASSO regressions, higher FGRS for major depression, bipolar disorder, and suicide death were associated with lower odds of UDI relative to unambiguous suicide (OR = 0.91–0.95), while those for alcohol and drug use disorders, ADHD, and criminal behavior were associated with higher odds of UDI relative to unambiguous suicide (OR = 1.04–1.12). When the corresponding phenotypic registration status for these outcomes was included in a subsequent model, the associations were attenuated and of small magnitude, but many remained different from OR = 1. Conclusions: Aggregate genetic differences between unambiguous suicide decedents and UDI deaths are small, particularly when accounting for psychiatric comorbidity, but in some cases, statistically significant. These findings suggest that different analytic treatment of UDI deaths may be warranted depending on the research question. Replication in other samples, and using molecular genetic data, is necessary.
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| 4. |
- Edwards, Alexis C., et al.
(författare)
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Oral contraceptive use and risk of suicidal behavior among young women
- 2022
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Ingår i: Psychological Medicine. - 0033-2917. ; 52:9, s. 1710-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background. Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association. Methods. We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide. Results. In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73-2.78 after 1 month of use, and 1.25-1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period. Conclusions. Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.
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| 5. |
- Ji, Jianguang, et al.
(författare)
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Response to Commentary by Pedersen et al.
- 2013
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Ingår i: Schizophrenia Bulletin. - : Oxford University Press (OUP). - 1745-1701 .- 0586-7614. ; 39:3, s. 506-506
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Karriker-Jaffe, Katherine J., et al.
(författare)
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Chains of risk for alcohol use disorder : Mediators of exposure to neighborhood deprivation in early and middle childhood
- 2018
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Ingår i: Health and Place. - : Elsevier BV. - 1353-8292. ; 50, s. 16-26
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Tidskriftsartikel (refereegranskat)abstract
- Our goal was to test a cascade model to identify developmental pathways, or chains of risk, from neighborhood deprivation in childhood to alcohol use disorder (AUD) in young adulthood. Using Swedish general population data, we examined whether exposure to neighborhood deprivation during early and middle childhood was associated with indicators of social functioning in adolescence and emerging adulthood, and whether these were predictive of AUD. Structural equation models showed exposure to neighborhood deprivation was associated with lower school achievement during adolescence, poor social functioning during emerging adulthood, and the development of AUD for both males and females. Understanding longitudinal pathways from early exposure to adverse environments to later AUD can inform prevention and intervention efforts.
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| 7. |
- Karriker-Jaffe, Katherine J., et al.
(författare)
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Young men's behavioral competencies and risk of alcohol use disorder in emerging adulthood : Early protective effects of parental education
- 2021
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Ingår i: Development and Psychopathology. - 0954-5794. ; 33:1, s. 135-148
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Tidskriftsartikel (refereegranskat)abstract
- We investigate how early exposure to parental externalizing behaviors (EB) may contribute to development of alcohol use disorders (AUD) in young adulthood, testing a developmental cascade model focused on competencies in three domains (academic, conduct, and work) in adolescence and emerging adulthood, and examining whether high parental education can buffer negative effects of parental EB and other early risk factors. We use data from 451,054 Swedish-born men included in the national conscript register. Structural equation models showed parental EB was associated with academic and behavioral problems during adolescence, as well as with lower resilience, more criminal behavior, and reduced social integration during emerging adulthood. These pathways led to elevated rates of AUD in emerging and young adulthood. Multiple groups analysis showed most of the indirect pathways from parental EB to AUD were present but buffered by higher parental education, suggesting early life experiences and competencies matter more for young men from lower socioeconomic status (SES) families than from higher SES families. Developmental competencies in school, conduct, and work are important precursors to the development of AUD by young adulthood that are predicted by parental EB. Occupational success may be an overlooked source of resilience for young men from low-SES families.
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| 8. |
- Kendler, Kenneth S., et al.
(författare)
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Genetic liability to suicide attempt, suicide death, and psychiatric and substance use disorders on the risk for suicide attempt and suicide death : A Swedish national study
- 2023
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Ingår i: Psychological Medicine. - 0033-2917. ; 53:4, s. 1639-1648
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Tidskriftsartikel (refereegranskat)abstract
- Background How does genetic liability to suicide attempt (SA), suicide death (SD), major depression (MD), bipolar disorder (BD), schizophrenia (SZ), alcohol use disorder (AUD), and drug use disorder (DUD) impact on risk for SA and SD? Methods In the Swedish general population born 1932-1995 and followed through 2017 (n = 7 661 519), we calculate family genetic risk scores (FGRS) for SA, SD, MD, BD, SZ, AUD, and DUD. Registration for SA and SD was assessed from Swedish national registers. Results In univariate and multivariate models predicting SA, FGRS were highest for SA, AUD, DUD, and MD. In univariate models predicting SD, the strongest FGRS were AUD, DUD, SA, and SD. In multivariate models, the FGRS for SA and AUD were higher in predicting SA while the FGRS for SD, BD, and SZ were higher in predicting SD. Higher FGRS for all disorders significantly predicted both younger age at first SA and frequency of attempts. For SD, higher FGRS for MD, AUD, and SD predicted later age at SD. Mediation of FGRS effects on SA and SD was more pronounced for SD than SA, strongest for AUD, DUD, and SZ FGRS and weakest for MD. Conclusions FGRS for both SA and SD and for our five psychiatric disorders impact on risk for SA and SD in a complex manner. While some of the impact of genetic risk factors for psychiatric disorders on risk for SA and SD is mediated through developing the disorders, these risks also predispose directly to suicidal behaviors.
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| 9. |
- Moscati, Arden, et al.
(författare)
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Life is pain : Fibromyalgia as a nexus of multiple liability distributions
- 2023
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Ingår i: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. - 1552-4841. ; 192:7-8, s. 171-182
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Tidskriftsartikel (refereegranskat)abstract
- Fibromyalgia is a complex disease of unclear etiology that is complicated by difficulties in diagnosis, treatment, and clinical heterogeneity. To clarify this etiology, healthcare-based data are leveraged to assess the influences on fibromyalgia in several domains. Prevalence is less than 1% of females in our population register data, and about 1/10th that in males. Fibromyalgia often presents with co-occurring conditions including back pain, rheumatoid arthritis, and anxiety. More comorbidities are identified with hospital-associated biobank data, falling into three broad categories of pain-related, autoimmune, and psychiatric disorders. Selecting representative phenotypes with published genome-wide association results for polygenic scoring, we confirm genetic predispositions to psychiatric, pain sensitivity, and autoimmune conditions show associations with fibromyalgia, although these may differ by ancestry group. We conduct a genome-wide association analysis of fibromyalgia in biobank samples, which did not result in any genome-wide significant loci; further studies with increased sample size are necessary to identify specific genetic effects on fibromyalgia. Overall, fibromyalgia appears to have strong clinical and likely genetic links to several disease categories, and could usefully be understood as a composite manifestation of these etiological sources.
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| 10. |
- 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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