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- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
- Stranneheim, Henrik, et al.
(författare)
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Rapid pulsed whole genome sequencing for comprehensive acute diagnostics of inborn errors of metabolism
- 2014
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15, s. 1090-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Massively parallel DNA sequencing (MPS) has the potential to revolutionize diagnostics, in particular for monogenic disorders. Inborn errors of metabolism (IEM) constitute a large group of monogenic disorders with highly variable clinical presentation, often with acute, nonspecific initial symptoms. In many cases irreversible damage can be reduced by initiation of specific treatment, provided that a correct molecular diagnosis can be rapidly obtained. MPS thus has the potential to significantly improve both diagnostics and outcome for affected patients in this highly specialized area of medicine. Results: We have developed a conceptually novel approach for acute MPS, by analysing pulsed whole genome sequence data in real time, using automated analysis combined with data reduction and parallelization. We applied this novel methodology to an in-house developed customized work flow enabling clinical-grade analysis of all IEM with a known genetic basis, represented by a database containing 474 disease genes which is continuously updated. As proof-of-concept, two patients were retrospectively analysed in whom diagnostics had previously been performed by conventional methods. The correct disease-causing mutations were identified and presented to the clinical team after 15 and 18 hours from start of sequencing, respectively. With this information available, correct treatment would have been possible significantly sooner, likely improving outcome. Conclusions: We have adapted MPS to fit into the dynamic, multidisciplinary work-flow of acute metabolic medicine. As the extent of irreversible damage in patients with IEM often correlates with timing and accuracy of management in early, critical disease stages, our novel methodology is predicted to improve patient outcome. All procedures have been designed such that they can be implemented in any technical setting and to any genetic disease area. The strategy conforms to international guidelines for clinical MPS, as only validated disease genes are investigated and as clinical specialists take responsibility for translation of results. As follow-up in patients without any known IEM, filters can be lifted and the full genome investigated, after genetic counselling and informed consent.
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| 6. |
- Alzubaidi, H., et al.
(författare)
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Statistical Analysis of Gravel Road Rating
- 2002
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Ingår i: The international journal of pavement engineering. - Nottingham. - 1029-8436 .- 1477-268X. ; 3:1, s. 35-42
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Andersson, Hedvig, et al.
(författare)
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Young adults looking back at their experiences of treatment and care for nonsuicidal self-injury during adolescence: a qualitative study
- 2024
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Ingår i: Child and Adolescent Psychiatry and Mental Health. - : BMC. - 1753-2000. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNonsuicidal self-injury (NSSI) is associated with stigma, and negative attitudes among healthcare professionals toward NSSI have been reported. A person-centered approach that focuses on how individuals with lived experience of NSSI perceive the treatment and care they receive is invaluable in reducing barriers to help-seeking and improving treatment and mental healthcare services. The aim of the current qualitative study was to explore the perceptions of young adults when they look back upon their experiences of psychiatric treatment for NSSI during adolescence.MethodsTwenty-six individuals with lived experience of NSSI who were in contact with child and adolescent psychiatry during adolescence were interviewed. The interviews were analyzed using thematic analysis.ResultsThree main themes were developed: Changed perceptions in retrospect, The importance of a collaborative conceptualization and Lasting impression of the relationship. Participants' perception of themselves as well as the treatment changed over time. The importance of a joint understanding of NSSI and an agreed-upon treatment focus was emphasized. The relationship to the mental health professionals, and experiences of how NSSI was communicated, were salient several years later.ConclusionsHealthcare professionals need to communicate about NSSI in a respectful manner and include the perspective of the adolescent with lived experience of NSSI in a joint conceptualization of NSSI and treatment focus.
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| 9. |
- Berglund, Andreas
(författare)
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Prognos av vägars bärförmåga vid tjällossningen : användning av temperatur som nyckeltal
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The global trend towards a warmer climate and temperatures near or just above 0 °C during winter months, will most likely be more common in future. One of the consequences of this climate change could, in a worst-case scenario, be freezing and thawing over a significant part of the winter with corresponding road bearing capacity problems. Bearing capacity problems may lead to increased costs to society when heavy traffic is forced to change route or carry less weight. In addition, road maintenance costs will increase. According to pulp industry calculations, this industry sector will face additional costs in the range of 510-590 Million SEK every year due to road bearing capacity problems. In addition to this, the costs related to the rapidly growing bio fuel industry will be added. If a reliable forecast of load-bearing capacity problems and potential load restrictions on roads can be found, it would be cost effective for road administration and society. This text presents the content of the licentiate work is presented and in what report more information could be found. One aspect of frost damage on roads that is highlighted in the thesis is decision making when conducting a road inventory. In a study conducted within the licentiate work it was shown that the results from different actors performing frost inventory on the same road stretch can vary a lot. There should be efforts made to reduce the individual dependence when performing a road inventory. The main part of the licentiate work deals with a model for the prediction of bearing capacity problems on roads. The work gives an idea of the possibility to use the temperature based model used in Minnesota, USA in Sweden. The evaluation is done by comparing falling weight deflectometer (FWD) test results with the results from the temperature based forecast model. When comparing the FWD results: AREA-parameter and subgrade modulus with results from the Minnesota model, the subgrade modulus seems to have the greatest agreement with the forecast model. However, they both seem to show the overall development of low bearing capacity during thaw. The overall conclusion about the temperature based forecast model is that it seems to give fairly good results and work well. It will work better if it can be further calibrated but it has some flaws if the temperature seesaws around 0 °C. The forecast model should, despite this, be able to assist road holders in Sweden as a planning tool, when dealing with bearing capacity problems during thaw.
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