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- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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| 2. |
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| 3. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 4. |
- Watson, H. J., et al.
(författare)
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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8, s. 1207-
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Tidskriftsartikel (refereegranskat)abstract
- Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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| 6. |
- Zhaunerchyk, Vitali, et al.
(författare)
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Disentangling formation of multiple-core holes in aminophenol molecules exposed to bright X-FEL radiation
- 2015
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Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 48:24
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Tidskriftsartikel (refereegranskat)abstract
- Competing multi-photon ionization processes, some leading to the formation of double core hole states, have been examined in 4-aminophenol. The experiments used the linac coherent light source (LCLS) x-ray free electron laser, in combination with a time-of-flight magnetic bottle electron spectrometer and the correlation analysis method of covariance mapping. The results imply that 4-aminophenol molecules exposed to the focused x-ray pulses of the LCLS sequentially absorb more than two x-ray photons, resulting in the formation of multiple core holes as well as in the sequential removal of photoelectrons and Auger electrons (so-called PAPA sequences).
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| 7. |
- Sgouros, D., et al.
(författare)
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Dermatoscopic features of thin (<= 2 mm Breslow thickness) vs. thick (>2 mm Breslow thickness) nodular melanoma and predictors of nodular melanoma versus nodular non-melanoma tumours: a multicentric collaborative study by the International Dermoscopy Society
- 2020
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 34:11, s. 2541-2547
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Tidskriftsartikel (refereegranskat)abstract
- Background Thin nodular melanoma (NM) often lacks conspicuous melanoma-specific dermatoscopic criteria and escapes clinical detection until it progresses to a thicker and more advanced tumour. Objective To investigate the dermatoscopic morphology of thin (<= 2 mm Breslow thickness) vs. thick (>2 mm) NM and to identify dermatoscopic predictors of its differential diagnosis from other nodular tumours. Methods Retrospective, morphological case-control study, conducted on behalf of the International Dermoscopy Society. Dermatoscopic images of NM and other nodular tumours from 19 skin cancer centres worldwide were collected and analysed. Results Overall, 254 tumours were collected (69 NM of Breslow thickness <= 2 mm, 96 NM >2 mm and 89 non-melanoma nodular lesions). Light brown coloration (50.7%) and irregular brown dots/globules (42.0%) were most frequently observed in <= 2 mm NMs. Multivariate analysis revealed that dotted vessels (3.4-fold), white shiny streaks (2.9-fold) and irregular blue structureless area (2.4-fold) were predictors for thinner NM compared to non-melanoma nodular tumours. Overall, irregular blue structureless area (3.4-fold), dotted vessels (4.6-fold) and serpentine vessels (1.9-fold) were predictors of all NM compared to non-melanoma nodular lesions. Limitations Absence of a centralized, consensus pathology review and cases selected form tertiary centres maybe not reflecting the broader community. Conclusions Our study sheds light into the dermatoscopic morphology of thin NM in comparison to thicker NM and could provide useful clues for its differential diagnosis from other non-melanoma nodular tumours.
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| 8. |
- Thomas, Richard D., et al.
(författare)
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DESIREE : Physics with cold stored ion beams
- 2015
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Ingår i: DR2013. - : EDP Sciences. ; 84, s. 01004-01004
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Konferensbidrag (refereegranskat)abstract
- Here we will briefly describe the commissioning of the Double ElectroStatic Ion Ring ExpEriment (DESIREE) facility at Stockholm University, Sweden. This device uses purely electrostatic focussing and deflection elements and allows ion beams of opposite charge to be confined under extreme high vacuum and cryogenic conditions in separate rings and then merged over a common straight section. This apparatus allows for studies of interactions between cations and anions at very low and well-defined centre-of-mass energies (down to a few meV) and at very low internal temperatures (down to a few K).
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| 9. |
- Petruzzo, P., et al.
(författare)
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VCA in the Era of the COVID-19 Pandemic
- 2022
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 106:4, s. 690-692
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Sehgal, R., et al.
(författare)
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Indole-3-propionic acid, a gut-derived tryptophan metabolite, associates with hepatic fibrosis
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Gut microbiota-derived metabolites play a vital role in maintenance of human health and progression of disorders, including obesity and type 2 diabetes (T2D). Indole-3-propionic acid (IPA), a gut-derived tryptophan metabolite, has been recently shown to be lower in individuals with obesity and T2D. IPA’s beneficial effect on liver health has been also explored in rodent and cell models. In this study, we investigated the association of IPA with human liver histology and transcriptomics, and the potential of IPA to reduce hepatic stellate cell activation in vitro. Methods: A total of 233 subjects (72% women; age 48.3 ± 9.3 years; BMI 43.1 ± 5.4 kg/m2) undergoing bariatric surgery with detailed liver histology were included. Circulating IPA levels were measured using LC-MS and liver transcriptomics with total RNA-sequencing. LX-2 cells were used to study hepatoprotective effect of IPA in cells activated by TGF-β1. Results: Circulating IPA levels were found to be lower in individuals with liver fibrosis compared to those without fibrosis (p = 0.039 for all participants; p = 0.013 for 153 individuals without T2D). Accordingly, levels of circulating IPA associated with expression of 278 liver transcripts (p < 0.01) that were enriched for the genes regulating hepatic stellate cells (HSCs) activation and hepatic fibrosis signaling. Our results suggest that IPA may have hepatoprotective potential because it is able to reduce cell adhesion, cell migration and mRNA gene expression of classical markers of HSCs activation in LX-2 cells (all p < 0.05). Conclusion: The association of circulating IPA with liver fibrosis and the ability of IPA to reduce activation of LX-2 cells suggests that IPA may have a therapeutic potential. Further molecular studies are needed to investigate the mechanisms how IPA can ameliorate hepatic fibrosis. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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