| 1. |
- Schmidt, Amand F., et al.
(författare)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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| 2. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 3. |
- Lorenz, K, et al.
(författare)
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Al1xInxN/GaN bilayers: Structure,morphology, and optical properties
- 2010
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Ingår i: Physica status solidi. B, Basic research. - : Wiley. - 0370-1972 .- 1521-3951. ; 247:7, s. 1740-1746
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Tidskriftsartikel (refereegranskat)abstract
- High quality Al1xInxN/GaN bilayers, grown by metal organic chemical vapor deposition (MOCVD), were characterized using structural and optical techniques. Compositional analysis was performed using Rutherford backscattering spectrometry(RBS) and elastic recoil detection analysis (ERDA). The InN molar fraction x decreased approximately linearly with increasing growth temperature and ranged from x¼0.13 to0.24. Up tox¼0.20 the layers grow pseudomorphically to GaN with good crystalline quality. These layers show a smoothsurface with V-shaped pits. Two layers with InN contents around 24% showed partial strain relaxation. However, themechanisms leading to relaxation of compressive strain arevery different in the two samples grown both at similartemperature but with different growth rates. One sample shows a decreased c/a ratio, as expected for relaxation of the compressive strain, while In was shown to be homogeneouslydistributed with depth. The other sample started to grow withx¼0.24 but relaxed mainly by reduction of the incorporated InN content towards the lattice-match composition of x0.17. Both samples have an increased surface roughness. All samples show strong Al1xInxN band edge luminescence with large bowing parameter and Stokes’ shifts.
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| 4. |
- Lorenz, K, et al.
(författare)
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Europium doping of zincblende GaN by ion implantation
- 2009
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 105:11, s. 113507-
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Tidskriftsartikel (refereegranskat)abstract
- Eu was implanted into high quality cubic (zincblende) GaN (ZB-GaN) layers grown by molecular beam epitaxy. Detailed structural characterization before and after implantation was performed by x-ray diffraction (XRD) and Rutherford backscattering/channeling spectrometry. A low concentration (<10%) of wurtzite phase inclusions was observed by XRD analysis in as-grown samples with their (0001) planes aligned with the {111} planes of the cubic lattice. Implantation of Eu causes an expansion of the lattice parameter in the implanted region similar to that observed for the c-lattice parameter of wurtzite GaN (W-GaN). For ZB-GaN:Eu, a large fraction of Eu ions is found on a high symmetry interstitial site aligned with the 〈110〉 direction, while a Ga substitutional site is observed for W-GaN:Eu. The implantation damage in ZB-GaN:Eu could partly be removed by thermal annealing, but an increase in the wurtzite phase fraction was observed at the same time. Cathodoluminescence, photoluminescence (PL), and PL excitation spectroscopy revealed several emission lines which can be attributed to distinct Eu-related optical centers in ZB-GaN and W-GaN inclusions.
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