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- Mishra, A., et al.
(author)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Journal article (peer-reviewed)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.
(author)
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Influence of atmospheric circulation patterns on urban air quality during the winter
- 2015
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In: Atmospheric Pollution Research. - 1309-1042. ; 6:2, s. 278-285
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Journal article (peer-reviewed)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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- Karlsson, Per Erik, 1957, et al.
(author)
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Increasing risk for negative ozone impacts on vegetation in northern Sweden
- 2007
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In: Environmental Pollution. ; 150, s. 96-106
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Journal article (peer-reviewed)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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- Olofson, K. Frans G., 1976, et al.
(author)
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Urban aerosol evolution and particle formation during wintertime temperature inversions
- 2009
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In: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 43, s. 340-346
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Journal article (peer-reviewed)abstract
- Aerosol temporal and spatial distributions during wintertime temperature inversions in Gothenburg, Sweden, have been characterized by ground-based and airborne particle measurements combined with lidar measurements. Ground inversions frequently developed during evenings and nights with stable cold conditions, and the low wintertime insolation often resulted in near neutral boundary layer conditions during day-time. Under these conditions ground level aerosol concentrations peaked during morning rush hours and often remained relatively high throughout the day due to inefficient ventilation. The particle number concentrations decreased slowly with increasing altitude within the boundary layer, and measurements slightly above the boundary layer suggested limited entrainment of polluted air into the free troposphere. High concentrations of ultrafine particles were observed throughout the boundary layer up to altitudes of 1100 m, which suggested that nucleation took place within the residual layer during the night and early morning. Recently formed particles were also observed around midday when the layer near ground was ventilated by mixing into the boundary layer, which indicated that ultrafine particles were either transported down from the residual layer to ground level or formed when the polluted surface layer mixed with the cleaner air above.
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- Tang, Lin, 1972
(author)
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Regional and local surface ozone variations in relation to meteorological conditions in Sweden
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Air quality is strongly dependent on meteorological conditions. Atmospheric circulation encapsulates general information about local meteorological variables to some extent, and can serve as an explanatory variable for air quality at a regional or local scale. Numerical models are another useful tool for understanding the influence of meteorological factors on the chemical and physical processes involved in regional and local air quality variations. The aims of this thesis have been to: (1) investigate regional surface ozone and its correlation to atmospheric circulations by making use of synoptic weather types in southern Sweden; (2) compare numerical models performances in simulating urban meteorological conditions and apply a numerical model to urban air quality study for Gothenburg. The study confirmed the influences of synoptic circulation on regional ozone concentrations by relating the Lamb Weather Types (LWTs) to surface ozone variations. Anticyclones, associated with atmospheric stagnation, tend to create whirling air masses and short trajectories from the European continent, which leads to effective long-range transport, enhanced local ozone photochemical production, and high-ozone levels. Cyclones, on the other hand, can also create high level ozone through frontal passages and enhanced vertical mixing. At the same time, the frequencies of cyclones and anticyclones in this region are highly anti-correlated, making cyclone frequency a skilful predictor of high ozone events. The frequency of cyclones over the past 150 years shows a high variability and showed significantly downward trend. Given the constant conditions from other factors for example emission, continuous decrease in the frequency of cyclones indicates the more occurrences of high-ozone events in southern Sweden. A numerical model - The Air Quality Model (TAPM) - was used to simulate the complex wind system and other meteorological variables needed for air quality applications in the Gothenburg area. Compared with The PSU/NCAR fifth-generation Mesoscale Model (MM5), TAPM is able to better reproduce near-surface air temperature and wind system in Gothenburg. Both MM5 and TAPM can simulate night-time vertical temperature gradient well, but underestimate daytime vertical temperature gradient and the occurrences of low wind speed situation at night. TAPM was then used to reproduce NOx−O3 reactions and investigate the wind speed effect on spatial differences of NO2 concentrations in the polluted urban landscape. TAPM satisfactorily simulated the relation of NO, NO2 and ozone as well as the site differences for different wind speed categories. However, TAPM underestimated NO at certain sites due to local scale sitespecific conditions and missing emissions from nearby roads and other emission sources.
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