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Sökning: WFRF:(Hensch T)

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2.
  • Demenais, Florence, et al. (författare)
  • Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks
  • 2018
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 50:1, s. 42-
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.
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3.
  • Gorski, Mathias, et al. (författare)
  • 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.
  • 2017
  • Ingår i: Scientific Reports. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.
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4.
  • Beelen, Rob, et al. (författare)
  • Effects of long-term exposure to air pollution on natural-cause mortality : an analysis of 22 European cohorts within the multicentre ESCAPE project
  • 2014
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 383:9919, s. 785-795
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants.METHODS: We used data from 22 European cohort studies, which created a total study population of 367 251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2·5 μm (PM2·5), less than 10 μm (PM10), and between 10 μm and 2·5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis.FINDINGS: The total study population consisted of 367 251 participants who contributed 5 118 039 person-years at risk (average follow-up 13·9 years), of whom 29 076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2·5 of 1·07 (95% CI 1·02-1·13) per 5 μg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0·95). HRs for PM2·5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m(3) (HR 1·06, 95% CI 1·00-1·12) or below 20 μg/m(3) (1·07, 1·01-1·13).INTERPRETATION: Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value.FUNDING: European Community's Seventh Framework Program (FP7/2007-2011).
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5.
  • Beelen, Rob, et al. (författare)
  • Long-term exposure to air pollution and cardiovascular mortality : an analysis of 22 European cohorts
  • 2014
  • Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 25:3, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death.METHODS: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and 10 μm to 2.5 μm (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates.RESULTS: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 μg/m and for PM10, 1.22 (0.91-1.63) per 10 μg/m.CONCLUSION: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.
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6.
  • de Hoogh, Kees, et al. (författare)
  • Comparing land use regression and dispersion modelling to assess residential exposure to ambient air pollution for epidemiological studies
  • 2014
  • Ingår i: Environment International. - 0160-4120 .- 1873-6750. ; 73, s. 382-392
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Land-use regression (LUR) and dispersion models (DM) are commonly used for estimating individual air pollution exposure in population studies. Few comparisons have however been made of the performance of these methods.OBJECTIVES: Within the European Study of Cohorts for Air Pollution Effects (ESCAPE) we explored the differences between LUR and DM estimates for NO2, PM10 and PM2.5.METHODS: The ESCAPE study developed LUR models for outdoor air pollution levels based on a harmonised monitoring campaign. In thirteen ESCAPE study areas we further applied dispersion models. We compared LUR and DM estimates at the residential addresses of participants in 13 cohorts for NO2; 7 for PM10 and 4 for PM2.5. Additionally, we compared the DM estimates with measured concentrations at the 20-40 ESCAPE monitoring sites in each area.RESULTS: The median Pearson R (range) correlation coefficients between LUR and DM estimates for the annual average concentrations of NO2, PM10 and PM2.5 were 0.75 (0.19-0.89), 0.39 (0.23-0.66) and 0.29 (0.22-0.81) for 112,971 (13 study areas), 69,591 (7) and 28,519 (4) addresses respectively. The median Pearson R correlation coefficients (range) between DM estimates and ESCAPE measurements were of 0.74 (0.09-0.86) for NO2; 0.58 (0.36-0.88) for PM10 and 0.58 (0.39-0.66) for PM2.5.CONCLUSIONS: LUR and dispersion model estimates correlated on average well for NO2 but only moderately for PM10 and PM2.5, with large variability across areas. DM predicted a moderate to large proportion of the measured variation for NO2 but less for PM10 and PM2.5.
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8.
  • Sigmundsson, F., et al. (författare)
  • Segmented lateral dyke growth in a rifting event at Bardarbunga volcanic system, Iceland
  • 2015
  • Ingår i: Nature. - 0028-0836. ; 517:7533, s. 191-U158
  • Tidskriftsartikel (refereegranskat)abstract
    • Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long(1). Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens(2-4), or magma flowing vertically into dykes from an underlying source(5,6), with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Bardarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System(GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Bardarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Bardarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.
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10.
  • Beelen, Rob, et al. (författare)
  • Natural-Cause Mortality and Long-Term Exposure to Particle Components : An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project
  • 2015
  • Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 525-533
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Objectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter ( PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. Results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200ng/m(3)). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
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