| 1. |
- Winkler, TW, et al.
(författare)
-
Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
-
Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
|
|
| 2. |
- 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.
|
|
| 3. |
- Lumbers, R. T., et al.
(författare)
-
The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
-
Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
|
|
| 4. |
- Olivecrona, Henrik, et al.
(författare)
-
A new CT method for measuring cup orientation after total hip arthroplasty : A study of 10 patients
- 2004
-
Ingår i: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 75:3, s. 252-260
-
Tidskriftsartikel (refereegranskat)abstract
- Background It is difficult to assess the orientation of the acetabular component on routine radiographs. We present a method for determining the spatial orientation of the acetabular component after total hip arthroplasty (THA) using computed tomography. Patients and methods Two CT-scans, 10 min apart, were obtained from each of 10 patients after THA. Using locally developed software, two independent examiners measured the orientation of the acetabular component in relation to the pelvis. The measurements were repeated after one week. To be independent of the patient position during scanning, the method involved two steps. Firstly, a 3D volumetric image of the pelvis was brought into a standard pelvic orientation, then the orientation of the acetabular component was measured. The orientation of the acetabular component was expressed as operative anteversion and inclination relative to an internal pelvic reference coordinate system. To evaluate precision, we compared measurements across pairs of CT volumes between observers and trials. Results Mean absolute interobserver angle error was 2.3degrees for anteversion (range 0-6.6degrees), and 1.1degrees for inclination (range 0-4.6degrees). For interobserver measurements, the precision, defined as one standard deviation, was 2.9degrees for anteversion, and 1.5degrees for inclination. A Student's West showed that the overall differences between the examiners, trials, and cases were not significant. Data were normally distributed and were not dependent on examiner or trial. Interpretation We conclude that the implant angles of the acetabular component in relation to the pelvis could be detected repeatedly using CT, independently of patient positioning.
|
|
| 5. |
- Adolfson, Malin, et al.
(författare)
-
Monetary policy trade-offs in an estimated open-economy DSGE model
- 2014
-
Ingår i: Journal of Economic Dynamics and Control. - : Elsevier BV. - 0165-1889 .- 1879-1743. ; 42, s. 33-49
-
Tidskriftsartikel (refereegranskat)abstract
- This paper studies the trade-offs between stabilizing CPI inflation and alternative measures of the output gap in Ramses, the Riksbank's estimated dynamic stochastic general equilibrium (DSGE) model of a small open economy. Our main finding is that the trade-off between stabilizing CPI inflation and the output gap strongly depends on which concept of potential output in the output gap between output and potential output is used in the loss function. If potential output is defined as a smooth trend this trade-off is much more pronounced compared to the case when potential output is defined as the output level that would prevail if prices and wages were flexible.
|
|
| 6. |
- Adolfson, Malin, et al.
(författare)
-
Optimal Money Policy in an Operational Medium-Sized DSGE Model
- 2011
-
Ingår i: Journal of Money, Credit and Banking. - : Wiley. - 0022-2879 .- 1538-4616. ; 43, s. 1287-1331
-
Tidskriftsartikel (refereegranskat)abstract
- We show how to construct optimal policy projections in Ramses, the Riksbank's open-economy medium-sized dynamic stochastic general equilibrium model for forecasting and policy analysis. Bayesian estimation of the parameters of the model indicates that they are relatively invariant to alternative policy assumptions and supports our view that the model parameters may be regarded as unaffected by the monetary policy specification. We discuss how monetary policy, and in particular the choice of output gap measure, affects the transmission of shocks. Finally, we use the model to assess the recent Great Recession in the world economy and how its impact on the economic development in Sweden depends on the conduct of monetary policy. This provides an illustration on how Rames incoporates large international spillover effects.
|
|
| 7. |
- Aggarwal, MM, et al.
(författare)
-
Centrality dependence of charged-neutral particle fluctuations in 158A (GeVPb)-Pb-208+Pb-208 collisions
- 2003
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 67:4
-
Tidskriftsartikel (refereegranskat)abstract
- Results on the study of localized fluctuations in the multiplicity of charged particles and photons produced in 158A GeV/c Pb+Pb collisions are presented for varying centralities. The charged versus neutral particle multiplicity correlations in common phase space regions of varying azimuthal sizes are analyzed by two different methods. Various types of mixed events are constructed to probe fluctuations arising from different sources. The measured results are compared to those from simulations and from mixed events. The comparison indicates the presence of nonstatistical fluctuations in both the charged particle and photon multiplicities in limited azimuthal regions. However, no correlated charged-neutral fluctuations, a possible signature of formation of disoriented chiral condensates, are observed. An upper limit on the production of disoriented chiral condensates is set.
|
|
| 8. |
- Aggarwal, M. M., et al.
(författare)
-
Event-by-event charged-neutral fluctuations in Pb plus Pb collisions at 158 A GeV
- 2011
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 701:3, s. 300-305
-
Tidskriftsartikel (refereegranskat)abstract
- Charged particles and photons have been measured in central Pb + Pb collisions at 158 A GeV in a common (eta-phi)-phase space region in the WA98 experiment at the CERN SPS. The measured distributions have been analyzed to quantify the frequency with which phase space regions of varying sizes have either small or large neutral pion fraction. The measured results are compared with VENUS model simulated events and with mixed events. Events with both large and small charged-neutral fluctuations are observed to occur more frequently than expected statistically, as deduced from mixed events, or as predicted by model simulations, with the difference becoming more prominent with decreasing size of the A Delta eta-Delta phi region. (C) 2011 Elsevier B.V. All rights reserved.
|
|
| 9. |
- Aggarwal, M. M., et al.
(författare)
-
Photon and eta production in p plus Pb and p plus C collisions at root(NN)-N-S=17.4 GeV
- 2013
-
Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 898, s. 14-23
-
Tidskriftsartikel (refereegranskat)abstract
- Measurements of direct photon production in p + Pb and p + C collisions at root(NN)-N-s = 17.4 GeV are presented. Upper limits on the direct photon yield as a function of p(T) are derived and compared to the results for Pb + Pb collisions at root(NN)-N-s = 17.3 GeV. The production of the eta meson, which is an important input to the direct photon signal extraction, has been determined in the eta -> 2 gamma channel for p + C collisions at root(NN)-N-s = 17.4 GeV. (c) 2012 Elsevier B.V. All rights reserved.
|
|
| 10. |
- Aggarwal, M. M., et al.
(författare)
-
Pion freeze-out time in Pb plus Pb collisions at 158 AGeV/c studied via pi(-)/pi(+) and K-/K+ ratios
- 2006
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 48:2, s. 343-352
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of the final state Coulomb interaction on particles produced in Pb + Pb collisions at 158AGeV/c has been investigated in the WA98 experiment through the study of the pi(-)/pi(+) and K-/K+ ratios measured as a function of T-m- (m)0. While the ratio for kaons shows no significant T-m dependence, the pi(-)/pi(+) ratio is enhanced at small T-m - (m)0 values with an enhancement that increases with centrality. A silicon pad detector located near the target is used to estimate the contribution of hyperon decays to the pi(-)/pi(+) ratio. The comparison of results with predictions of the RQMD model in which the Coulomb interaction has been incorporated allows to place constraints on the time of the pion freeze-out.
|
|
