| 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. |
- Akbarian, S, et al.
(författare)
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The PsychENCODE project
- 2015
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Ingår i: Nature neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 18:12, s. 1707-1712
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Berkowitz, Staci A., et al.
(författare)
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Childhood body mass index in adolescent-onset anorexia nervosa
- 2016
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Ingår i: International Journal of Eating Disorders. - : Wiley. - 1098-108X .- 0276-3478. ; 49:11, s. 1002-1009
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Although weight history is relevant in predicting eating disorder symptom severity, little is known about its role in the etiology of anorexia nervosa (AN). This study aimed to determine whether BMI or BMI trajectory differed between individuals who later developed adolescent-onset AN and a comparison group of HCs between school grades 1 through 6.METHOD: This study was based on longitudinal data that identified 51 adolescents with AN and 51 matched HCs. Cases were identified through community screening in Sweden and included individuals born in 1969 through 1977. Measured weights and heights were retrieved and BMIs and weight trajectories of the AN and HC groups were compared using growth curve analysis. Main outcome measures included measured BMI and BMI trajectories from grades 1-6. Secondary outcomes examined included ponderal index at birth and maternal body weight.RESULTS: Individuals who later developed AN had higher BMIs than HCs between grades 1 and 6, by an average of 1.42 BMI-units. There was no difference in rate of weight gain between groups. Ponderal index at birth was higher for the AN as compared with HC group. Maternal weight did not differ significantly between groups.DISCUSSION: These findings, combined with those previously reported on the premorbid BMIs of those with bulimia nervosa, suggest that a predisposition toward elevated premorbid BMIs during childhood characterizes those who later develop anorexia or bulimia nervosa. These findings are consistent with a transdiagnostic perspective and suggest shared risk factors for AN and obesity. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016).
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| 5. |
- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 6. |
- Witt, Ashley A., et al.
(författare)
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Weight Suppression and Body Mass Index Interact to Predict Long-Term Weight Outcomes in Adolescent-Onset Anorexia Nervosa
- 2014
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Ingår i: Journal of Consulting and Clinical Psychology. - : American Psychological Association (APA). - 0022-006X .- 1939-2117. ; 82:6, s. 1207-1211
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Tidskriftsartikel (refereegranskat)abstract
- Research on anorexia nervosa (AN) has emphasized the importance of low absolute body weight, but emerging research suggests the importance of also considering low body weight relative to an individual's highest premorbid weight (weight suppression; WS). Objective: We investigated whether body mass index and WS at lowest weight (BMI-LW and WS-LW) among adolescents with AN predicted BMI at 6-, 10-, or 18-year follow-up, duration of AN, or total eating disorder duration, including time during which criteria were met for bulimia nervosa or eating disorder not otherwise specified. Method: Forty-seven cases of AN identified through community screening in Sweden were included. Weight and height data were collected from medical records, school nurse charts, and study follow-up assessments. Results: Higher WS-LW was associated with higher BMI at 6-year and 10-year follow-up, and this effect was strongest among those with the lowest BMI-LW values. BMI-LW and WS-LW were positively associated with BMI at 18-year follow-up, but there was no significant interaction. There was no significant association between WS-LW and AN duration or eating disorder duration, although eating disorder duration was longer among those with higher BMI-LW, controlling for WS-LW. Conclusions: Absolute and relative weight status interact to predict weight outcomes in AN over the long term. Results suggest that BMI and WS may be more relevant to the prediction of long-term weight outcomes than to the persistence of other eating disorder symptoms.
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