| 1. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 2. |
- Winkler, TW, et al.
(author)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Journal article (peer-reviewed)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.
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| 3. |
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| 4. |
- Ilieva, S., et al.
(author)
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Coulomb excitation of neutron-rich Cd isotopes
- 2014
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 89:1
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Journal article (peer-reviewed)abstract
- The isotopes (122),(124),Cd-126 were studied in a "safe" Coulomb-excitation experiment at the radioactive ion-beam facility REX-ISOLDE at CERN. The reduced transition probabilities B(E2; 0(g. s)(vertical bar) -> 2(1)(+)) and limits for the quadrupole moments of the first 2(+) excited states in the three isotopes were determined. The onset of collectivity in the vicinity of the Z = 50 and N = 82 shell closures is discussed by comparison with shell model and beyond mean-field calculations.
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| 5. |
- Teumer, A, et al.
(author)
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Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
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Journal article (peer-reviewed)abstract
- Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
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| 6. |
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| 7. |
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| 8. |
- Wuttke, Matthias, et al.
(author)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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In: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Journal article (peer-reviewed)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.
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| 9. |
- Pelisek, J, et al.
(author)
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Biobanking: Objectives, Requirements, and Future Challenges-Experiences from the Munich Vascular Biobank
- 2019
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In: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:2
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Journal article (peer-reviewed)abstract
- Collecting biological tissue samples in a biobank grants a unique opportunity to validate diagnostic and therapeutic strategies for translational and clinical research. In the present work, we provide our long-standing experience in establishing and maintaining a biobank of vascular tissue samples, including the evaluation of tissue quality, especially in formalin-fixed paraffin-embedded specimens (FFPE). Our Munich Vascular Biobank includes, thus far, vascular biomaterial from patients with high-grade carotid artery stenosis (n = 1567), peripheral arterial disease (n = 703), and abdominal aortic aneurysm (n = 481) from our Department of Vascular and Endovascular Surgery (January 2004–December 2018). Vascular tissue samples are continuously processed and characterized to assess tissue morphology, histological quality, cellular composition, inflammation, calcification, neovascularization, and the content of elastin and collagen fibers. Atherosclerotic plaques are further classified in accordance with the American Heart Association (AHA), and plaque stability is determined. In order to assess the quality of RNA from FFPE tissue samples over time (2009–2018), RNA integrity number (RIN) and the extent of RNA fragmentation were evaluated. Expression analysis was performed with two housekeeping genes—glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB)—using TaqMan-based quantitative reverse-transcription polymerase chain reaction (qRT)-PCR. FFPE biospecimens demonstrated unaltered RNA stability over time for up to 10 years. Furthermore, we provide a protocol for processing tissue samples in our Munich Vascular Biobank. In this work, we demonstrate that biobanking is an important tool not only for scientific research but also for clinical usage and personalized medicine.
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| 10. |
- Dent, E., et al.
(author)
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International Clinical Practice Guidelines for Sarcopenia (ICFSR) : Screening, Diagnosis and Management
- 2018
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In: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 22:10, s. 1148-1161
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Journal article (peer-reviewed)abstract
- Objectives: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR).Methods: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process.Recommendations: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.
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