| 11. |
- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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| 12. |
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| 13. |
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| 14. |
- Grun, E., et al.
(författare)
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The 2016 Feb 19 outburst of comet 67P/CG : an ESA Rosetta multi-instrument study
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S220-S234
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Tidskriftsartikel (refereegranskat)abstract
- On 2016 Feb 19, nine Rosetta instruments serendipitously observed an outburst of gas and dust from the nucleus of comet 67P/Churyumov-Gerasimenko. Among these instruments were cameras and spectrometers ranging from UV over visible to microwave wavelengths, in situ gas, dust and plasma instruments, and one dust collector. At 09: 40 a dust cloud developed at the edge of an image in the shadowed region of the nucleus. Over the next two hours the instruments recorded a signature of the outburst that significantly exceeded the background. The enhancement ranged from 50 per cent of the neutral gas density at Rosetta to factors > 100 of the brightness of the coma near the nucleus. Dust related phenomena (dust counts or brightness due to illuminated dust) showed the strongest enhancements (factors > 10). However, even the electron density at Rosetta increased by a factor 3 and consequently the spacecraft potential changed from similar to-16 V to -20 V during the outburst. A clear sequence of events was observed at the distance of Rosetta ( 34 km from the nucleus): within 15 min the Star Tracker camera detected fast particles (similar to 25 m s(-1)) while 100 mu m radius particles were detected by the GIADA dust instrument similar to 1 h later at a speed of 6 m s(-1). The slowest were individual mm to cm sized grains observed by the OSIRIS cameras. Although the outburst originated just outside the FOV of the instruments, the source region and the magnitude of the outburst could be determined.
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| 15. |
- Kueppers, Michael, et al.
(författare)
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Triple F-a comet nucleus sample return mission
- 2009
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 809-847
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Tidskriftsartikel (refereegranskat)abstract
- The Triple F (Fresh From the Fridge) mission, a Comet Nucleus Sample Return, has been proposed to ESA's Cosmic Vision program. A sample return from a comet enables us to reach the ultimate goal of cometary research. Since comets are the least processed bodies in the solar system, the proposal goes far beyond cometary science topics (like the explanation of cometary activity) and delivers invaluable information about the formation of the solar system and the interstellar molecular cloud from which it formed. The proposed mission would extract three sample cores of the upper 50 cm from three locations on a cometary nucleus and return them cooled to Earth for analysis in the laboratory. The simple mission concept with a touch-and-go sampling by a single spacecraft was proposed as an M-class mission in collaboration with the Russian space agency ROSCOSMOS.
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| 16. |
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| 17. |
- 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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| 18. |
- 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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| 19. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 20. |
- Fulle, M., et al.
(författare)
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Evolution Of The Dust Size Distribution Of Comet 67P/Churyumov-Gerasimenko From 2.2 Au To Perihelion
- 2016
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 821:1
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Tidskriftsartikel (refereegranskat)abstract
- The Rosetta probe, orbiting Jupiter-family comet 67P/Churyumov-Gerasimenko, has been detecting individual dust particles of mass larger than 10(-10) kg by means of the GIADA dust collector and the OSIRIS Wide Angle Camera and Narrow Angle Camera since 2014 August and will continue until 2016 September. Detections of single dust particles allow us to estimate the anisotropic dust flux from 67P, infer the dust loss rate and size distribution at the surface of the sunlit nucleus, and see whether the dust size distribution of 67P evolves in time. The velocity of the Rosetta orbiter, relative to 67P, is much lower than the dust velocity measured by GIADA, thus dust counts when GIADA is nadir-pointing will directly provide the dust flux. In OSIRIS observations, the dust flux is derived from the measurement of the dust space density close to the spacecraft. Under the assumption of radial expansion of the dust, observations in the nadir direction provide the distance of the particles by measuring their trail length, with a parallax baseline determined by the motion of the spacecraft. The dust size distribution at sizes > 1 mm observed by OSIRIS is consistent with a differential power index of -4, which was derived from models of 67P's trail. At sizes <1 mm, the size distribution observed by GIADA shows a strong time evolution, with a differential power index drifting from -2 beyond 2 au to -3.7 at perihelion, in agreement with the evolution derived from coma and tail models based on ground-based data. The refractory-to-water mass ratio of the nucleus is close to six during the entire inbound orbit and at perihelion.
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