| 1. |
- Wuttke, Matthias, et al.
(författare)
-
A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
-
Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
|
|
| 2. |
- Bin, Ma, et al.
(författare)
-
Dielectric Properties and Resistance to Corona and Ozone of Epoxy Compositions Filled with Micro- and Nano-fillers
- 2009
-
Ingår i: Annual Report - Conference on Electrical Insulation and Dielectric Phenomena. ; , s. -380
-
Konferensbidrag (refereegranskat)abstract
- This paper describes activities aiming to evaluate and compare the resistance to a prolonged corona and ozone exposure for a range of epoxy based compositions filled with micro- and nano-fillers of silica at different proportions. It has been earlier shown for this system that substitution of 5 wt% of micro-filler by nano-filler slightly improved mechanical properties, yielding an increase in Young's modulus, tensile strength and elongation at break. At the same time, the toughness of the systems decreased with the addition of nano-fillers indicating a poor particle-matrix interaction, which was in accordance with the prior art claiming that this interaction is weaker in case of SiO 2 nano-particles, as for example compared to Al 2O 3 nano-particles. For the exposure to corona and ozone a methodology employing a multiple-needle electrode system was used, as recommended by CIGRE working group WG D1.14. Measurements of surface resistivity, bulk resistivity as well as dielectric response (DR) at broad frequency range (10 -4-10 3 Hz) were performed on new samples of the investigated compositions and after each of two sequences of the corona-ozone treatment, lasting 100hours each. It was found that the long-term corona-ozone exposure had obvious effect on surface resistivity for all the compositions investigated and the contents of the micro- and nano-fillers played a significant role in the observed changes. On the other hand, bulk resisitivity, dielectric permittivity as well as dissipation factor, all being the properties of material bulk, did not exhibit high sensitivity to the exposure.
|
|
| 3. |
|
|
| 4. |
- Graf, Alexander, et al.
(författare)
-
Joint optimization of land carbon uptake and albedo can help achieve moderate instantaneous and long-term cooling effects
- 2023
-
Ingår i: Communications Earth and Environment. - 2662-4435. ; 4:1
-
Tidskriftsartikel (refereegranskat)abstract
- Both carbon dioxide uptake and albedo of the land surface affect global climate. However, climate change mitigation by increasing carbon uptake can cause a warming trade-off by decreasing albedo, with most research focusing on afforestation and its interaction with snow. Here, we present carbon uptake and albedo observations from 176 globally distributed flux stations. We demonstrate a gradual decline in maximum achievable annual albedo as carbon uptake increases, even within subgroups of non-forest and snow-free ecosystems. Based on a paired-site permutation approach, we quantify the likely impact of land use on carbon uptake and albedo. Shifting to the maximum attainable carbon uptake at each site would likely cause moderate net global warming for the first approximately 20 years, followed by a strong cooling effect. A balanced policy co-optimizing carbon uptake and albedo is possible that avoids warming on any timescale, but results in a weaker long-term cooling effect.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Mahmoodi, Bakhtawar K., et al.
(författare)
-
Association of Factor V Leiden With Subsequent Atherothrombotic Events A GENIUS-CHD Study of Individual Participant Data
- 2020
-
Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 142:6, s. 546-555
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16];I-2=28%;P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
|
|
| 8. |
- Patel, Riyaz S., et al.
(författare)
-
Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
-
Ingår i: Circulation. - 2574-8300. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
|
|
| 9. |
- Patel, Riyaz S., et al.
(författare)
-
Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
-
Ingår i: Circulation. - 2574-8300. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
|
|
| 10. |
- Tang, Angela Che Ing, et al.
(författare)
-
Detection and attribution of an anomaly in terrestrial photosynthesis in Europe during the COVID-19 lockdown
- 2023
-
Ingår i: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 903
-
Tidskriftsartikel (refereegranskat)abstract
- Carbon dioxide (CO2) uptake by plant photosynthesis, referred to as gross primary production (GPP) at the ecosystem level, is sensitive to environmental factors, including pollutant exposure, pollutant uptake, and changes in the scattering of solar shortwave irradiance (SWin) − the energy source for photosynthesis. The 2020 spring lockdown due to COVID-19 resulted in improved air quality and atmospheric transparency, providing a unique opportunity to assess the impact of air pollutants on terrestrial ecosystem functioning. However, detecting these effects can be challenging as GPP is influenced by other meteorological drivers and management practices. Based on data collected from 44 European ecosystem-scale CO2 flux monitoring stations, we observed significant changes in spring GPP at 34 sites during 2020 compared to 2015–2019. Among these, 14 sites showed an increase in GPP associated with higher SWin, 10 sites had lower GPP linked to atmospheric and soil dryness, and seven sites were subjected to management practices. The remaining three sites exhibited varying dynamics, with one experiencing colder and rainier weather resulting in lower GPP, and two showing higher GPP associated with earlier spring melts. Analysis using the regional atmospheric chemical transport model (LOTOS-EUROS) indicated that the ozone (O3) concentration remained relatively unchanged at the research sites, making it unlikely that O3 exposure was the dominant factor driving the primary production anomaly. In contrast, SWin increased by 9.4 % at 36 sites, suggesting enhanced GPP possibly due to reduced aerosol optical depth and cloudiness. Our findings indicate that air pollution and cloudiness may weaken the terrestrial carbon sink by up to 16 %. Accurate and continuous ground-based observations are crucial for detecting and attributing subtle changes in terrestrial ecosystem functioning in response to environmental and anthropogenic drivers.
|
|
