| 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. |
- Weinhofer, Isabelle, et al.
(författare)
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Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy.
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
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| 4. |
- Andam, Berima, 1986, et al.
(författare)
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Florida: Feature LOcatIon DAshboard for extracting and visualizing feature traces
- 2017
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Ingår i: Proceedings of the Eleventh International Workshop on Variability Modelling of Software-intensive Systems, VaMoS 2017. - New York, NY, USA : ACM. ; Part F126227, s. 100-107
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Konferensbidrag (refereegranskat)abstract
- © 2017 Copyright held by the owner/author(s). Features are high-level, domain-specific abstractions over implementation artifacts. Developers use them to communicate and reason about a system, in order to maintain and evolve it. These activities, however, require knowing the locations of features - a common challenge when a system has many developers, many (cloned) variants, or a long lifespan. We believe that embedding feature-location information into software artifacts via annotations eases typical feature-related engineering tasks, such as modifying and removing features, or merging cloned features into a product line. However, regardless of where such annotations stem from - whether embedded by developers when writing code, or retroactively recovered using a feature-location technique - tool support is needed for developers to exploit such annotations. In this tool demonstration, we present a lightweight tool that extracts annotations from software artifacts, aggregates and processes them, and visualizes feature-related information for developers. Views, such as which files implement a specific feature, are presented on different levels of abstraction. Feature metrics, such as feature size, feature scattering, feature tangling, and numbers of feature authors, are also presented. Our tool also incorporates an information-retrieval-based feature-location technique to retroactively recover feature locations.
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| 5. |
- Lotz, Jannik, et al.
(författare)
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Microservice Architectures for Advanced Driver Assistance Systems: A Case-Study
- 2019
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Ingår i: Proceedings - 2019 IEEE International Conference on Software Architecture - Companion, ICSA-C 2019. ; , s. 45-52
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Konferensbidrag (refereegranskat)abstract
- The technological advancements of recent years have steadily increased the complexity of vehicle-internal software systems, and the ongoing development towards autonomous driving will further aggravate this situation. This is leading to a level of complexity that is pushing the limits of existing vehicle software architectures and system designs. By changing the software structure to a service-based architecture, companies in other domains successfully managed the rising complexity and created a more agile and future-oriented development process. This paper presents a case-study investigating the feasibility and possible effects of changing the software architecture for a complex driver assistance function to a microservice architecture. The complete procedure is described, starting with the description of the software-environment and the corresponding requirements, followed by the implementation, and the final testing. In addition, this paper provides a high-level evaluation of the microservice architecture for the automotive use-case. The results show that microservice architectures can reduce complexity and time-consuming process steps and make the automotive software systems prepared for upcoming challenges as long as the principles of microservice architectures are carefully followed.
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| 6. |
- Möller, Per Werner, et al.
(författare)
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The Effects of Vasoconstriction And Volume Expansion on Veno-Arterial ECMO Flow
- 2019
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Ingår i: Shock. - 1073-2322. ; 51:5, s. 650-658
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Tidskriftsartikel (refereegranskat)abstract
- Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is gaining widespread use in the treatment of severe cardiorespiratory failure. Blood volume expansion is commonly used to increase ECMO flow (QECMO), with risk of positive fluid balance and worsening prognosis. We studied the effects of vasoconstriction on recruitment of blood volume as an alternative for increasing QECMO, based on the concepts of venous return.In a closed chest, centrally cannulated porcine preparation (n = 9) in ventricular fibrillation and VA-ECMO with vented left atrium, mean systemic filling pressure (MSFP), and venous return driving pressure (VRdP) were determined in Euvolemia, during Vasoconstriction (norepinephrine 0.05, 0.125, and 0.2 μg/kg/min) and after Volume Expansion (3 boluses of 10 mL/kg Ringer's lactate). Maximum achievable QECMO was examined.Vasoconstriction and Volume Expansion both increased maximum achievable QECMO, delivery of oxygen (DO2), and MSFP, but right atrial pressure increased in parallel. VRdP did not change. The vascular elastance curve was shifted to the left by Vasoconstriction, with recruitment of stressed volume. It was shifted to the right by Volume Expansion with direct expansion of stressed volume. Volume Expansion decreased resistance to venous return and pump afterload.In a circulation completely dependent on ECMO support, maximum achievable flow directly depended on the vascular factors governing venous return-i.e., closing conditions, stressed vascular volume and the elastance and resistive properties of the vasculature. Both treatments increased maximum achievable ECMO flow at stable DO2, via increases in stressed volume by different mechanisms. Vascular resistance and pump afterload decreased with Volume Expansion.
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| 7. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 8. |
- Wallerius, Magnus L., et al.
(författare)
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Socially induced stress and behavioural inhibition in response to angling exposure in rainbow trout
- 2019
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Ingår i: Fisheries Management and Ecology. - : Wiley. - 0969-997X .- 1365-2400. ; 26:6, s. 611-620
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that fish can learn to avoid angling gear after experiencing a catch-and-release event, that is, after a private hooking experience. However, the possible importance of social information cues and their influence on an individual's vulnerability to angling remains largely unexplored, that is, social experience of a conspecific capture. The effects of private and social experience of hooking on the stress response of fish and subsequent catch rates were examined. Hatchery-reared rainbow trout, Oncorhynchus mykiss (Walbaum), were implanted with heart rate loggers and experimentally subjected to private or social experience of hooking. Private and social experience of angling induced an increased heart rate in fish compared with naive control fish. While private experience of hooking explained most of the reduced vulnerability to capture, no clear evidence was found that social experience of hooking affected angling vulnerability in fish that had never been hooked before. While both private and social experiences of angling constitute significant physiological stressors for rainbow trout, only the private experience reduces an individual's vulnerability to angling and in turn affecting population-level catchability.
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| 9. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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