| 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. |
- Diehl, Roland, et al.
(författare)
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Early Ni-56 decay gamma rays from SN2014J suggest an unusual explosion
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6201, s. 1162-1165
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Tidskriftsartikel (refereegranskat)abstract
- Type Ia supernovae result from binary systems that include a carbon-oxygen white dwarf, and these thermonuclear explosions typically produce 0.5 solar mass of radioactive Ni-56. The Ni-56 is commonly believed to be buried deeply in the expanding supernova cloud. In SN2014J, we detected the lines at 158 and 812 kiloelectron volts from Ni-56 decay (time similar to 8.8 days) earlier than the expected several-week time scale, only similar to 20 days after the explosion and with flux levels corresponding to roughly 10% of the total expected amount of Ni-56. Some mechanism must break the spherical symmetry of the supernova and at the same time create a major amount of Ni-56 at the outskirts. A plausible explanation is that a belt of helium from the companion star is accreted by the white dwarf, where this material explodes and then triggers the supernova event.
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| 4. |
- Foley, Ryan J., et al.
(författare)
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THE FIRST MAXIMUM-LIGHT ULTRAVIOLET THROUGH NEAR-INFRARED SPECTRUM OF A TYPE Ia SUPERNOVA
- 2012
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Ingår i: THE ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 753:1, s. L5-
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Tidskriftsartikel (refereegranskat)abstract
- We present the first maximum-light ultraviolet (UV) through near-infrared (NIR) Type Ia supernova (SN Ia) spectrum. This spectrum of SN 2011iv was obtained nearly simultaneously by the Hubble Space Telescope at UV/optical wavelengths and the Magellan Baade telescope at NIR wavelengths. These data provide the opportunity to examine the entire maximum-light SN Ia spectral energy distribution. Since the UV region of an SN Ia spectrum is extremely sensitive to the composition of the outer layers of the explosion, which are transparent at longer wavelengths, this unprecedented spectrum can provide strong constraints on the composition of the SN ejecta, and similarly the SN explosion and progenitor system. SN 2011iv is spectroscopically normal, but has a relatively fast decline (Delta m(15)(B) = 1.69 +/- 0.05 mag). We compare SN 2011iv to other SNe Ia with UV spectra near maximum light and examine trends between UV spectral properties, light-curve shape, and ejecta velocity. We tentatively find that SNe with similar light-curve shapes but different ejecta velocities have similar UV spectra, while those with similar ejecta velocities but different light-curve shapes have very different UV spectra. Through a comparison with explosion models, we find that both a solar-metallicity W7 and a zero-metallicity delayed-detonation model provide a reasonable fit to the spectrum of SN 2011iv from the UV to the NIR.
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| 5. |
- Rasmark Roepke, Emma, et al.
(författare)
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Reliability of recurrent pregnancy loss diagnosis coding in the Swedish national patient register : A validation study
- 2019
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 11, s. 375-381
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Swedish National Patient Registry (NPR) is a nationwide registry that is used extensively for epidemiological research. Using the NPR, we recently found a recurrent pregnancy loss (RPL) incidence of 650/100,000 (0.65%) pregnant women in Sweden. It is of great importance that the quality of the coding is good and reliable in order to use NPR data for research. To specifically study RPL in Sweden, a general validation of this diagnosis in the NPR is needed. Objective: To validate the diagnosis of RPL, defined as ≥3 consecutive miscarriages before 22 gestational weeks, recorded in the NPR and assess how registered miscarriages were verified clinically (ultrasound or urine/serum hCG) by reviewing the medical records. Materials and methods: In a cohort of 6,852 women diagnosed with RPL in Sweden, during 2003-2012, a total of 238 complete medical records from 38 hospitals were reviewed. A power calculation estimated that 228 medical records had to be reviewed for a positive predictive value (PPV) of 85% (95% CI) with a power of 90%. The ICD-10 diagnoses used for RPL were N96.9 and O26.2. Results: The diagnosis of RPL was confirmed in 202 out of 238 medical records resulting in a PPV of 85% (95% CI 78-89%) out of which 59% were verified with ultrasound whereas 35% were verified only by urine/serum hCG. Conclusion: The Swedish NPR is a valuable tool for epidemiological research. We found a high PPV of RPL in the NPR, supporting the use of these data for future research.
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| 6. |
- Roepke, Emma Rasmark, et al.
(författare)
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Women with a history of recurrent pregnancy loss are a high-risk population for adverse obstetrical outcome : A retrospective cohort study
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:2, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to late pregnancy complications. The aim of this retrospective register-based cohort study was to study the association between RPL and such disorders including pre-eclampsia, stillbirth, small for gestational age (SGA) birth, preterm birth and placental abruption. Women registered with childbirth(s) in the Swedish Medical Birth Register (MFR) were included in the cohort. Pregnancies of women diagnosed with RPL (exposed) in the National Patient Register (NPR), were compared with pregnancies of women without RPL (unexposed/reference). Obstetrical outcomes, in the first pregnancy subsequent to the diagnosis of RPL (n = 4971), were compared with outcomes in reference-pregnancies (n = 57,410). Associations between RPL and placental dysfunctional disorders were estimated by odds ratios (AORs) adjusting for confounders, with logistic regression. RPL women had an increased risk for pre-eclampsia (AOR 1.45; 95% CI; 1.24– 1.69), stillbirth <37 gestational weeks (GWs) (AOR 1.92; 95% CI; 1.22–3.02), SGA birth (AOR 1.97; 95% CI; 1.42–2.74), preterm birth (AOR 1.46; 95% CI; 1.20–1.77), and placental abruption <37 GWs (AOR 2.47; 95% CI; 1.62–3.76) compared with pregnancies by women without RPL. Women with RPL had an increased risk of pregnancy complications associated with placental dysfunction. This risk population is, therefore, in need of improved antenatal surveillance.
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| 7. |
- Schultebraucks, Katharina, et al.
(författare)
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Suicidal Imagery in Borderline Personality Disorder and Major Depressive Disorder.
- 2019
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Ingår i: Journal of Personality Disorders. - : Guilford Publications. - 0885-579X .- 1943-2763. ; , s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- A better understanding of suicidal behavior is important to detect suicidality in at-risk populations such as patients with borderline personality disorder (BPD), posttraumatic stress disorder (PTSD), and major depressive disorder (MDD). Suicidal tendencies are clinically assessed by verbal thoughts rather than by specifically asking about mental images. This study examines whether imagery and verbal thoughts about suicide occur and differ between patients with BPD with and without comorbid PTSD compared to patients with MDD (clinical controls). All patient groups experienced suicide-related images. Patients with BPD with comorbid PTSD reported significantly more vivid images than patients with MDD. Severity of suicidal ideation, number of previous suicide attempts, and childhood traumata were significantly associated with suicidal imagery across all patient groups. The authors demonstrate for the first time that suicide-related mental imagery occurs in BPD and is associated with suicidal ideation. This finding highlights the importance of assessing mental imagery related to suicide in clinical practice.
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| 8. |
- Seitenzahl, Ivo R., et al.
(författare)
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Three-dimensional simulations of gravitationally confined detonations compared to observations of SN 1991T
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592
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Tidskriftsartikel (refereegranskat)abstract
- The gravitationally confined detonation (GCD) model has been proposed as a possible explosion mechanism for Type Ia supernovae in the single-degenerate evolution channel. It starts with ignition of a deflagration in a single off-centre bubble in a near-Chandrasekhar-mass white dwarf. Driven by buoyancy, the deflagration flame rises in a narrow cone towards the surface. For the most part, the main component of the flow of the expanding ashes remains radial, but upon reaching the outer, low-pressure layers of the white dwarf, an additional lateral component develops. This causes the deflagration ashes to converge again at the opposite side, where the compression heats fuel and a detonation may be launched. We first performed five three-dimensional hydrodynamic simulations of the deflagration phase in 1.4 M-circle dot carbon/oxygen white dwarfs at intermediate-resolution (256(3) computational zones). We confirm that the closer the initial deflagration is ignited to the centre, the slower the buoyant rise and the longer the deflagration ashes takes to break out and close in on the opposite pole to collide. To test the GCD explosion model, we then performed a high-resolution (512(3) computational zones) simulation for a model with an ignition spot offset near the upper limit of what is still justifiable, 200 km. This high-resolution simulation met our deliberately optimistic detonation criteria, and we initiated a detonation. The detonation burned through the white dwarf and led to its complete disruption. For this model, we determined detailed nucleosynthetic yields by post-processing 10(6) tracer particles with a 384 nuclide reaction network, and we present multi-band light curves and time-dependent optical spectra. We find that our synthetic observables show a prominent viewing-angle sensitivity in ultraviolet and blue wavelength bands, which contradicts observed SNe Ia. The strong dependence on the viewing angle is caused by the asymmetric distribution of the deflagration ashes in the outer ejecta layers. Finally, we compared our model to SN 1991T. The overall flux level of the model is slightly too low, and the model predicts pre-maximum light spectral features due to Ca, S, and Si that are too strong. Furthermore, the model chemical abundance stratification qualitatively disagrees with recent abundance tomography results in two key areas: our model lacks low-velocity stable Fe and instead has copious amounts of high-velocity Ni-56 and stable Fe. We therefore do not find good agreement of the model with SN 1991T.
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