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- 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. |
- Felicetti, Roberto, 1972-
(författare)
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Run-Up Transient Analysis for Salient Pole Wound Field Synchronous Motors : Field winding and power electronics implications for a smoother and cooler asynchronous start
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Salient Pole Wound Field Synchronous Machines have better efficiency at full load than asynchronous machines of the same capability. Moreover, where asynchronous machines need inherently to draw a magnetizing current from the grid, Salient Pole Wound Field Synchronous Machines can work efficiently at unity power factor. When needed, their power factor can even turn leading in order to provide reactive power to the grid. It is well known, that the asynchronous machines performances deteriorate very quickly in presence of voltage drops, while the Wound Field Synchronous Machines prove to be capable of riding through voltage sags without stalling of falling out of step. Besides, for short-time overload, machines with a field winding can provide a pull-out torque even three times larger than the nominal one. Finally, when working as generators, Wound Field Synchronous Machines can perform a black starting where asynchronous machines cannot. Why are then asynchronous machines so successful in comparison to synchronous ones when used as motors? Robustness, low-maintenance, simplicity are the key-features that translate immediately in low fixed costs for asynchronous motors. But, even though lower variable costs for a synchronous motor should envisage a break-even starting form a given power rate on, there are still some technical issues to be overcome. A synchronous motor must be first sped-up to the synchronism for it to deliver mechanical power. And when it is directly on-line started like an asynchronous motor, it draws large reactive currents due to its large airgap. Therefore, additional means are needed for avoiding the motor overheating and voltage disturbances on the grid, such as autotransformers, transformers and reactors. Besides, in Salient Pole Wound Field Synchronous Machines. due to the inherent magnetic and electric rotor asymmetry, the starting asynchronous torque presents a nasty large pseudo-periodic ripple. In this work, a novel starting technique is presented, which mitigates all problems related to the run-up by means of a special rotor winding and excitation-system arrangement. The suggested start strategy is validated by an experimental test carried out on a build prototype and through a field-to-circuit coupled transient simulation. Since AC currents are essentially injected into the rotor winding during the machine start, in its first part the thesis explores what does happen in a winding traditionally designed for the direct current supply when an alternated current is injected into it by a power electronics device. To that end, changes in the main field winding parameters are firstly investigated, which take place under AC-supply. The obtained results make it possible to build a wide-band frequency electromagnetic model for the field winding. The model is useful for studying the potentially harmful voltage surges and voltage gradients triggered by fast rising/falling voltage-edges. Finally, within the specific application of the field current control and with the aim to prevent large voltage surges, the research provides some hints for the design of the field winding and for the coordination of the power electronics and the field winding properties.
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| 4. |
- Taranto, Philip, et al.
(författare)
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Landauer Versus Nernst : What is the True Cost of Cooling a Quantum System
- 2023
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Ingår i: PRX Quantum. - 2691-3399. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Thermodynamics connects our knowledge of the world to our capability to manipulate and thus to control it. This crucial role of control is exemplified by the third law of thermodynamics, Nernst's unattainability principle, which states that infinite resources are required to cool a system to absolute zero temperature. But what are these resources and how should they be utilized And how does this relate to Landauer's principle that famously connects information and thermodynamics We answer these questions by providing a framework for identifying the resources that enable the creation of pure quantum states. We show that perfect cooling is possible with Landauer energy cost given infinite time or control complexity. However, such optimal protocols require complex unitaries generated by an external work source. Restricting to unitaries that can be run solely via a heat engine, we derive a novel Carnot-Landauer limit, along with protocols for its saturation. This generalizes Landauer's principle to a fully thermodynamic setting, leading to a unification with the third law and emphasizes the importance of control in quantum thermodynamics.
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