| 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. |
- Beery, Thomas, et al.
(författare)
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Outdoor recreation and Covid-19 – : post pandemic consequences for nature area planning
- 2024
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Skriver Hansen, A, Beery, T., Stahl Olafsson, A., & Præstholm, S. (2022). Outdoor recreation and Covid-19 – post pandemic consequences for nature area planning. The Tenth Nordic Planning Research Symposium. August 2022. Aalborg, Danmark.
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| 4. |
- Chiang, Michael F., et al.
(författare)
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International Classification of Retinopathy of Prematurity, Third Edition
- 2021
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Ingår i: Ophthalmology. - : Elsevier. - 0161-6420 .- 1549-4713. ; 128:10, s. 51-68
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., antievascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system.Design: Review of evidence-based literature, along with expert consensus opinion. Participants: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men.Methods: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification.Main Outcome Measures: Consensus statement.Results: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae.Conclusions: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.
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| 5. |
- Jansson, Anna. K., et al.
(författare)
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Risk and mortality of testicular cancer in patients with neurodevelopmental or other psychiatric disorders
- 2023
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 128:12, s. 2261-2269
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBoth testicular germ cell tumours (TGCT) and neurodevelopmental disorders are associated with urogenital malformations. Few studies have investigated the association between psychiatric disorders and TGCT. We investigated whether history of any psychiatric or neurodevelopmental disorder is associated with increased risk or mortality of TGCT.MethodThis is a nested case-control study including 6166 TGCT patients diagnosed during 1992-2014, individually matched for age and calendar period to 61,660 controls. We calculated odds ratios (ORs) for the association between type of psychiatric diagnoses and TGCT risk. Among the cases, we used a cohort design and calculated hazard ratios (HRs) of the association between psychiatric diagnose and all-cause and TGCT-specific death.ResultsHistory of a neurodevelopmental disorder (attention deficit hyperactivity disorder, autism spectrum disorder and intellectual disabilities) was associated with an increased risk of seminoma (OR: 1.54; 1.09-2.19). Seminoma patients with neurodevelopmental disorders were younger (34 versus 38 years, p = 0.004) and had more stage IV disease (5.4% versus 1.2%) than those without. Psychiatric history overall was not associated with TGCT. Patient history of any psychiatric disorder was associated with an increased all-cause and TGCT-specific death.ConclusionsWe report an association between neurodevelopmental disorders and testicular seminoma, and an increased TGCT-specific mortality for TGCT patients with psychiatric disorders.
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| 6. |
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| 7. |
- Khani, Sajjad, et al.
(författare)
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Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function
- 2024
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Ingår i: Nature Metabolism. - 2522-5812.
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Tidskriftsartikel (refereegranskat)abstract
- Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5′ truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.
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| 8. |
- Palmer, Duncan S., et al.
(författare)
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Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia
- 2022
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 54:5, s. 541-547
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Tidskriftsartikel (refereegranskat)abstract
- We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10−9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD’s polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.
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| 9. |
- Pivodic, Aldina, 1978, et al.
(författare)
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Development and validation of a new clinical decision support tool to optimize screening for retinopathy of prematurity
- 2022
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Ingår i: British Journal of Ophthalmology. - : BMJ Publishing Group Ltd. - 0007-1161 .- 1468-2079. ; 106:11, s. 1573-1580
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Prematurely born infants undergo costly, stressful eye examinations to uncover the small fraction with retinopathy of prematurity (ROP) that needs treatment to prevent blindness. The aim was to develop a prediction tool (DIGIROP-Screen) with 100% sensitivity and high specificity to safely reduce screening of those infants not needing treatment. DIGIROP-Screen was compared with four other ROP models based on longitudinal weights.METHODS: Data, including infants born at 24-30 weeks of gestational age (GA), for DIGIROP-Screen development (DevGroup, N=6991) originate from the Swedish National Registry for ROP. Three international cohorts comprised the external validation groups (ValGroups, N=1241). Multivariable logistic regressions, over postnatal ages (PNAs) 6-14 weeks, were validated. Predictors were birth characteristics, status and age at first diagnosed ROP and essential interactions.RESULTS: ROP treatment was required in 287 (4.1%)/6991 infants in DevGroup and 49 (3.9%)/1241 in ValGroups. To allow 100% sensitivity in DevGroup, specificity at birth was 53.1% and cumulatively 60.5% at PNA 8 weeks. Applying the same cut-offs in ValGroups, specificities were similar (46.3% and 53.5%). One infant with severe malformations in ValGroups was incorrectly classified as not needing screening. For all other infants, at PNA 6-14 weeks, sensitivity was 100%. In other published models, sensitivity ranged from 88.5% to 100% and specificity ranged from 9.6% to 45.2%.CONCLUSIONS: DIGIROP-Screen, a clinical decision support tool using readily available birth and ROP screening data for infants born GA 24-30 weeks, in the European and North American populations tested can safely identify infants not needing ROP screening. DIGIROP-Screen had equal or higher sensitivity and specificity compared with other models. DIGIROP-Screen should be tested in any new cohort for validation and if not validated it can be modified using the same statistical approaches applied to a specific clinical setting.
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| 10. |
- Pivodic, Aldina, 1978, et al.
(författare)
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Individual Risk Prediction for Sight-Threatening Retinopathy of Prematurity Using Birth Characteristics
- 2020
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Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 138:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.
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| 11. |
- Skriver Hansen, Andreas, 1983, et al.
(författare)
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Outdoor recreation and Covid-19 – post pandemic consequences for nature area planning and management
- 2022
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Ingår i: PLANNORD 2022 Book of Abstracts - THE 10TH NORDIC PLANNING RESEARCH SYMPOSIUM. - Aalborg : Aalborg University.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- After the pandemic began in 2020, reports on increasing public interest in nature and outdoor recreation surfaced. Examples and discussions came from all corners of the Nordic countries and were echoed globally. Preliminary observations, especially among area managers of nature areas, saw a rapid increase in visitor numbers. In some areas, so many visitors arrived that it was difficult to manage all guests and activities. This presentation highlights key findings and reflections on consequences in the planning for outdoor recreation resources in post pandemic times. The base is three studies from Sweden and Denmark with a focus on outdoor recreation during the pandemic. Using surveys, interviews and PPGIS approaches, results reveal several important planning aspects based on trends observed during the pandemic, e.g. increased outdoor recreation participation, new activity trends and various changes in spatial preferences. It is suggested that particular attention should be given to several planning measures with spatial consequences, including more investment in and potential expansion of blue-green infrastructures and areas designated for recreation. Important is also securing easy access to recreational resources, both inside residential areas and in the vicinity of densely populated urban areas. More practical area-based planning considerations, such as increased parking facilities, better transportation option to and from nature areas, broadening of trails, more active use of zoning as well as intensified monitoring of ecological and social conditions are also highlighted. In the coming years, the work is of special interest to planners working with nature areas for outdoor recreation, who can use the presented knowledge to be inspired and structure future planning activities. Moreover, planners can take advantage of increased outdoor recreation participation during Covid-19 toward supporting a reverse of a general societal loss of nature experience. Finally, potentially positive outcomes of increased nature experience, such as an increased opportunity for connectedness to nature, may be able to focus planning on human nature experience in ways that support human well-being and the development of pro-environmental behaviors.
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| 12. |
- Tefre, Sondre, et al.
(författare)
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Endoscopic third ventriculostomy for adults with hydrocephalus: creating a prognostic model for success: protocol for a retrospective multicentre study (Nordic ETV)
- 2022
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarni et al created the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for EN and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. Methods and analysis The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients >= 18 years of age treated with EN at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. Ethics and dissemination The study is approved by appropriate ethics or patient safety boards in all participating countries.
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