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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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- Grundström, Maria, 1979, et al.
(författare)
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Influence of atmospheric circulation patterns on urban air quality during the winter
- 2015
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Ingår i: Atmospheric Pollution Research. - 1309-1042. ; 6:2, s. 278-285
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Tidskriftsartikel (refereegranskat)abstract
- Relationships between urban nitrogen dioxide (NO2) and atmospheric circulation at two spatial scales were studied for Southern Sweden. Lamb Weather Types (LWT) describe the circulation (scale: thousands of kilometers) including non–directional (cyclonic and anticyclonic) and directional types depending on the wind direction. LWTs with low wind speeds (anticyclonic, NW and N) were associated with strongly elevated [NO2], between 46–52% of the daily averages of NO2 exceeded the 60 μg m–3 air quality standard (AQS) when occurring during these LWTs. The lowest fractions of exceedances of NO2 AQS were generally observed for LWTs E, S, SW and W. A larger scale circulation (several thousands of kilometers) was represented by the North Atlantic Oscillation (NAO) affecting meteorology over middle and high latitudes in the Northern Hemisphere. While a negative NAO index (NAOI) favors stagnant high pressure weather over Northern Europe, a positive NAOI is often associated with windy conditions. High [NO2] was found to be frequent under negative NAOI. Additionally, larger fractions of exceedances of NO2 AQS were observed for the majority of LWTs occurring at negative NAOI. It’s concluded that both LWTs and NAOI had partly independent effects on the urban air quality in a North European city. These circulation indices can be useful tools for air pollution risk assessment and forecasting.
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| 10. |
- Karlsson, Per Erik, 1957, et al.
(författare)
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Increasing risk for negative ozone impacts on vegetation in northern Sweden
- 2007
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Ingår i: Environmental Pollution. ; 150, s. 96-106
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Tidskriftsartikel (refereegranskat)abstract
- Trends were found for increasing surface ozone concentrations during AprileSeptember in northern Sweden over the period 1990e2006 as well as for an earlier onset of vegetation growing season. The highest ozone concentrations in northern Sweden occurred in April and the ozone concentrations in April showed a strong increasing trend. A model simulation of ozone flux for Norway spruce indicated that the provisional ozone flux based critical level for forests in Europe is exceeded in northern Sweden. Future climate change would have counteracting effects on the stomatal conductance and needle ozone uptake, mediated on the one hand by direct effect of increasing air temperatures and on the other through increasing water vapour pressure difference between the needles and air. Thus, there is a substantial and increasing risk for negative impacts of ozone on vegetation in northern Sweden, related mainly to increasing ozone concentrations and an earlier onset of the growing season.
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