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- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 2. |
- Wightman, D. P., et al.
(författare)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Tidskriftsartikel (refereegranskat)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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| 3. |
- Bratland-Sanda, S., et al.
(författare)
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Physical activity in treatment units for eating disorders : Clinical practice and attitudes
- 2009
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Ingår i: Eating and Weight Disorders. - 1124-4909 .- 1590-1262. ; 14:2-3, s. E106-E112
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Physical activity (PA) in eating disorders (ED) may be harmful, but in a therapeutic setting also beneficial. The purpose of this survey was to examine these contradictory aspects of PA in ED specialist treatment settings. We examined whether 1) PA is assessed by the unit, 2) the units have guidelines for managing excessive PA, 3) the units have staff with higher education and special competence in PA and exercise science, 4) how units regard PA in ED, 5) whether regular PA is integrated in the treatment programs, and 6) how the units rate the role of PA in the treatment of ED compared with other mental disorders. METHODS: Of the 49 units located in Scandinavia and the United Kingdom, 41 (84%) responded to a questionnaire. RESULTS: In 28 units (68%) PA was assessed regularly. Excessive PA was considered a harmful symptom in ED, and most units reported guidelines to manage excessive PA. Thirty-two units included PA in their treatment programmes. Clinicians found PA most relevant in the treatment of obesity and, except for binge eating, less for ED. CONCLUSION: PA was more commonly integrated in treatment compared to previous studies. Future research should address how to manage excessive PA, and the potential beneficial role of PA in the treatment of ED. (Eating Weight Disord. 14: e106-e112, 2009). (C) 2009, Editrice Kurtis
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| 4. |
- Martinsen, V., et al.
(författare)
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pH effects of the addition of three biochars to acidic Indonesian mineral soils
- 2015
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Ingår i: Soil science and plant nutrition (Tokyo). - : Informa UK Limited. - 0038-0768 .- 1747-0765. ; 61:5, s. 821-834
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Tidskriftsartikel (refereegranskat)abstract
- Soil acidity may severely reduce crop production. Biochar (BC) may increase soil pH and cation exchange capacity (CEC) but reported effects differ substantially. In a systematic approach, using a standardized protocol on a uniquely large number set of 31 acidic soils, we quantified the effect of increasing amounts (0-30%; weight:weight) of three types of field-produced BCs (from cacao (Theobroma cacao. L.) shell, oil palm (Elaeis guineensis. Jacq.) shell and rice (Oryza sativa. L.) husk) on soil pH and CEC. Soils were sampled from croplands at Java, Sumatra and Kalimantan, Indonesia. All BCs caused a significant increase in mean soil pH with a stronger response and a greater maximum increase for the cacao shell BC addition, due to a greater acid neutralizing capacity (ANC) and larger amounts of extractable base cations. At 1% BC addition, corresponding to about 30tonsha(-1), the estimated increase in soil pH from the initial mean pH of 4.7 was about 0.5 units for the cacao shell BC, whereas this was only 0.05 and 0.04 units for the oil palm shell and rice husk BC, respectively. Besides depending on BC type, the increase in soil pH upon the addition of each of the three BCs was mainly dependent on soil CEC (low CEC resulting in stronger pH increase), and to a lesser extent on initial soil pH (higher initial pH resulting in stronger pH increase). Addition of BC also increased the amount of exchangeable base cations (cacao shell >> oil palm and rice husk) and CEC. Through this systematic screening of the effect of BC on pH and CEC of acidic soils, we show that a small addition of BC, in particular if made of cacao shell, to acidic agricultural soils increases soil pH and CEC. However, the response is highly dependent on the type, quality and amount of the added BC as well as on intrinsic soil properties, mainly CEC.
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