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- Mullins, N., et al.
(författare)
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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- McDonald, Matthew D., et al.
(författare)
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‘A Different Ball Game’ : Adaptation of a men’s health program for implementation in rural Australia
- 2023
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Ingår i: BMC Public Health. - London : BioMed Central (BMC). - 1471-2458. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Background: Men residing in rural areas are less likely to participate in weight management interventions than women, and few men-specific programs target rural areas. Aussie-Fans in Training (Aussie-FIT) is an evidence-based weight management intervention that uses professional Australian Football club affiliations and settings as a ‘hook’ to engage urban-residing men. The aim of this study is to report on how findings from rural stakeholder focus groups were used to inform the adaptation of Aussie-FIT for implementation in rural areas.Methods: Seven focus groups with stakeholders (n = 24) in three rural towns explored existing weight management and physical activity provisions, barriers and facilitators to engaging men, and considerations for adapting Aussie-FIT for implementation in rural contexts. Qualitative data were analysed using the framework approach. Adaptations made to the Aussie-FIT program and strategies to implement the program in rural contexts were reported using a structured framework.Results: Themes generated from our analysis include limited appealing services for men, Australian Football as a ‘common language’, the influence of the ‘smaller fishpond’(population), considerations for program inclusivity, and the importance of local partner organisations for sustainability. We adapted the recruitment and marketing strategies, delivery settings, football program theme and partnerships for rural implementation. Stakeholders advised that an Australian Football program theme without specific local club affiliations would be important to avoid alienating men with differing club allegiances or non-sporting backgrounds. A multi-component recruitment strategy utilising local trusted sources, and program marketing that aligns with masculine ideals were considered important by stakeholders in small communities where ‘people talk’.Conclusions: Rural areas were described as ‘a different ball game’ due to limited local services and resources in comparison to metropolitan areas. Study findings have synergies with previous studies undertaken in rural contexts including in relation to the power of word of mouth, the importance of trust, and local partner organisations. Findings have implications for engaging rural men in health interventions in rural contexts where professional sporting contexts are not available. Assessing the extent to which the adapted Aussie-FIT program can reach and engage men in rural Australia, and exploring the barriers and facilitators to delivering the program in rural contexts is required. © 2023, The Author(s).
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| 7. |
- McDonald, Matthew D., et al.
(författare)
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A systematic review examining socioeconomic factors in trials of interventions for men that report weight as an outcome
- 2022
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Ingår i: Obesity Reviews. - Chichester : John Wiley & Sons. - 1467-7881 .- 1467-789X. ; 23:7
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Forskningsöversikt (refereegranskat)abstract
- Weight management interventions designed specifically for men have become more common, but the extent to which socioeconomic factors are considered in trials of these interventions is unclear. We synthesized study characteristics, methods, and reporting of interventions with a behavioral component for men that report weight as an outcome, to establish the extent to which socioeconomic factors are considered during intervention design, conduct, and reporting. A comprehensive search was conducted on Medline, Embase, PsycINFO, and CENTRAL for studies published from January 2000 to July 2021. Thirty-six trials were included. Educational attainment (n = 24) was the most frequently reported socioeconomic characteristic, followed by working status (n = 14) and area level deprivation (n = 12). Seven studies did not report any socioeconomic characteristics. Most studies (n = 20) did not mention the socioeconomic profile of their samples in relation to study strengths or limitations. Few (n = 4) consulted with men from lower socioeconomic groups during intervention design. One study examined potential differential intervention effects across socioeconomic groups, with most not powered to do so. Recent feasibility trials (n = 3) targeting specific socioeconomic groups suggest a potential nascent towards a greater consideration of factors related to equity. To best inform public health policy related to health inequalities, greater consideration of socioeconomic factors is required in trials of men's weight management interventions. © 2022 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.
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| 8. |
- Sivaramakrishnan, Hamsini, et al.
(författare)
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Psychosocial outcomes of sport participation for middle-aged and older adults : a systematic review and meta-analysis
- 2021
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Ingår i: International Review of Sport and Exercise Psychology. - : Routledge. - 1750-984X .- 1750-9858.
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Tidskriftsartikel (refereegranskat)abstract
- © 2021 Informa UK Limited, trading as Taylor & Francis Group.Narrative reviews indicate psychological and social benefits of sport participation for the ageing population. However, no quantitative synthesis of quantitative studies on this topic has been conducted yet. We evaluated the magnitude and heterogeneity of the effects of sport participation on psychosocial outcomes for middle-aged and older adults (>35 years). Ten databases were searched in July 2020. Quantitative studies (k = 25) of middle-aged and older adults, measuring at least one psychosocial outcome of sport participation were included. Multilevel meta-analysis showed that the association between sport participation and psychosocial outcomes was small, yet significant. Moderation analyses revealed that the pooled effect differed according to outcome type; small to moderate associations were observed for social, positive psychological, perceived physical, and cognitive outcomes, but not for negative psychological outcomes. Risk of bias, assessed using the QualSyst tool, indicated low quality of evidence. Our findings suggest that sport participation is associated with multiple psychosocial benefits for middle-aged and older adults that appear invariant across participant-related and sport-related characteristics. We found no evidence of publication bias, but studies were underpowered and rated as low quality. Our review provides quantitative evidence for the psychosocial benefits of sport participation for adults, complementing existing qualitative research on this topic.
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