| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 3. |
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| 4. |
- Carey, J. L., et al.
(författare)
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Novel Arthroscopic Classification of Osteochondritis Dissecans of the Knee
- 2016
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Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 44:7, s. 1694-1698
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several systems have been proposed for classifying osteochondritis dissecans (OCD) of the knee during surgical evaluation. No single classification includes mutually exclusive categories that capture all of the salient features ov stability, chondral fissuring,0and fragment detachment. Furthermore, no study has assessed the reliability of these classification systems. Purpose: To determine the intra- and interobserver reliability of a novel, comprehensive arthroscopic classification system with mutually exclusivu OCD lesion types. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The Research in OsteoChondritis of the Knee (ROCK) study group developed a classification system for arthroscopic evaluation of OCD of the knee that includes 6 arthroscopic categories - 3 immobile types and 3 mobile types. To optymize comprehensibility and applycability, each was developed with a memorable name, a brief description, a line diagram corresponding to the archetypal arthroscopic appearance, and an arthroscopic photograph depicting this archetype. Thirty representative arthroscopic videos were evaluated by 10 orthopaedic surgeon raters, who classified each lesion. After 4 weeks, the raters again classified the OCD lesions depicted in the 30 videos in a new, randomly selected order. Reliability was assessed via the intraclass correlation coefficient (ICC). Results: The interobserver reliability of this novel arthroscopy classification was estimated by an ICC of 0.94 (95% CI, 0.91-0.97) for the first round and 0.95 (95% CI, 0.93-0.98) for the second round. According to the standards for the magnitude of the reliability coefficient of Altman, these ICCs indicate that interobserver reliability was very good. The intraobserver reliability was estimated by an ICC of 0.96 (95% CI, 0.95-0.97), which indicates that the intraobserver reliability was similarly very good. Conclusion: The ROCK OCD knee arthroscopy classification system demonstrated excellent intra- and interobserver reliability. In light of this reliability, this classification system may be used clinically and to facilitate future research, including multicenter studies for OCD. © American Orthopaedic Society for Sports Medicine.
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| 5. |
- Carey, L. M., et al.
(författare)
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STroke imAging pRevention and treatment (START): A longitudinal stroke cohort study: Clinical trials protocol
- 2015
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 10:4, s. 636-644
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Tidskriftsartikel (refereegranskat)abstract
- RationaleStroke and poststroke depression are common and have a profound and ongoing impact on an individual's quality of life. However, reliable biological correlates of poststroke depression and functional outcome have not been well established in humans. AimsOur aim is to identify biological factors, molecular and imaging, associated with poststroke depression and recovery that may be used to guide more targeted interventions. DesignIn a longitudinal cohort study of 200 stroke survivors, the START - STroke imAging pRevention and Treatment cohort, we will examine the relationship between gene expression, regulator proteins, depression, and functional outcome. Stroke survivors will be investigated at baseline, 24h, three-days, three-months, and 12 months poststroke for blood-based biological associates and at days 3-7, three-months, and 12 months for depression and functional outcomes. A sub-group (n=100), the PrePARE: Prediction and Prevention to Achieve optimal Recovery Endpoints after stroke cohort, will also be investigated for functional and structural changes in putative depression-related brain networks and for additional cognition and activity participation outcomes. Stroke severity, diet, and lifestyle factors that may influence depression will be monitored. The impact of depression on stroke outcomes and participation in previous life activities will be quantified. Study OutcomesClinical significance lies in the identification of biological factors associated with functional outcome to guide prevention and inform personalized and targeted treatments. Evidence of associations between depression, gene expression and regulator proteins, functional and structural brain changes, lifestyle and functional outcome will provide new insights for mechanism-based models of poststroke depression.
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| 6. |
- Hinwood, M., et al.
(författare)
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Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. Methods and analysis This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. Ethics and dissemination This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals.
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| 7. |
- Tse, T., et al.
(författare)
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Longitudinal changes in activity participation in the first year post-stroke and association with depressive symptoms
- 2019
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Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 41:21, s. 2548-2555
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Tidskriftsartikel (refereegranskat)abstract
- Research question: 1. Does activity participation improve over time in the first year after stroke? 2. What is the association of depressive symptoms on retained activity participation 12-months post-stroke adjusting for neurological stroke severity and age? 3. Is an improvement in activity participation associated with a decrease in depressive symptoms between 3- and 12-months post-stroke? Design: Longitudinal observational study of activity participation and depressive symptoms in ischemic stroke survivors. Participants: A total of 100 stroke survivors with mild neurological stroke severity. Methods: A total of 100 stroke survivors were recruited from five metropolitan hospitals and assessed at 3- and 12-months post-stroke using measures of activity participation (Activity Card Sort-Australia (ACS-Aus)) and depressive symptoms (Montgomery-Asberg Depression Rating Scale Structured Interview Guide (MADRS-SIGMA)). Results: There was a significant association between time (pre-stroke to 3-months post-stroke) and current activity participation (-5.2 activities 95% CI -6.8 to -3.5, p < 0.01) and time (pre-stroke to 12-months) and current activity participation (-2.1 activities 95% CI -3.7 to -0.5, p = 0.01). At 12-months post-stroke, a one-point increase in depressive symptoms was associated with a median decrease of 0.3% (95% CI -1.4% to -0.1%, p = 0.02) of retained overall activity participation, assuming similar neurological stroke severity and age. A decrease in depressive symptoms between 3- and 12-months post-stroke was associated with an improvement of 0.31 (95% CI -0.5 to -0.1, p = 0.01) in current activity participation. Conclusions: Activity participation improves during the first year of recovery post-stroke in stroke survivors with mild neurological stroke severity and is associated with depressive symptoms over time and at 12-months post-stroke.
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| 8. |
- Tse, T., et al.
(författare)
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Reduction in retained activity participation is associated with depressive symptoms 3 months after mild stroke: An observational cohort study
- 2017
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977. ; 49:2, s. 120-127
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To quantify the association of depressive symptoms with retained activity participation 3 months post-stroke, after adjusting for neurological stroke severity and age. Design: A cross-sectional observational study of retained activity participation and depressive symptoms in stroke survivors with ischaemic stroke. Participants: One hundred stroke survivors with mild neurological stroke severity. Methods: One hundred stroke survivors were recruited from 5 metropolitan hospitals and reviewed at 3 months post-stroke using measures of activity participation, Activity Card Sort-Australia, and depressive symptoms, Montgomery-Asberg Depression Rating Scale Structured Interview Guide (MADRS-SIGMA). Results: The median percentage of retained overall activity participation was 97%, (interquartile range 79-100%). Using multiple median regression, 1 point increase in the MADRS-SIGMA was associated with a median decrease of 0.7% (95% CI -1.4 to -0.1, p=0.02) of retained overall activity participation, assuming similar neurological stroke severity and age. Conclusion: The findings of this study establish the association of depressive symptoms with retained activity participation 3 months post-stroke in stroke survivors with mild neurological stroke severity. Clinical rehabilitation recommendations to enhance activity participation need to account for those with even mild depressive symptoms post-stroke.
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| 9. |
- Wei, C. T., et al.
(författare)
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Cryptic species in a colorful genus: Integrative taxonomy of the bush robins (Aves, Muscicapidae, Tarsiger) suggests two overlooked species
- 2022
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 175
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Tidskriftsartikel (refereegranskat)abstract
- Several cryptic avian species have been validated by recent integrative taxonomic efforts in the Sino-Himalayan mountains, indicating that avian diversity in this global biodiversity hotspot may be underestimated. In the present study, we investigated species limits in the genus Tarsiger, the bush robins, a group of montane forest specialists with high species richness in the Sino-Himalayan region. Based on comprehensive sampling of all 11 subspecies of the six currently recognized species, we applied an integrative taxonomic approach by combining multilocus, acoustic, plumage and morphometric analyses. Our results reveal that the isolated north-central Chinese populations of Tarsiger cyanurus, described as the subspecies albocoeruleus but usually considered invalid, is distinctive in genetics and vocalisation, but only marginally differentiated in morphology. We also found the Taiwan endemic T. indicus formosanus to be distinctive in genetics, song and morphology from T. i. indicus and T. i. yunnanensis of the Sino-Himalayan mountains. Moreover, Bayesian species delimitation using BPP suggests that both albocoeruleus and formosanus merit full species status. We propose their treatment as 'Qilian Bluetail' T. albocoeruleus and 'Taiwan Bush Robin' T. formosanus, respectively.
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| 10. |
- Abbott, Benjamin W., et al.
(författare)
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Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
- 2016
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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