Institution
Medical University of Graz
Education•Graz, Steiermark, Austria•
About: Medical University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Medicine. The organization has 5684 authors who have published 12349 publications receiving 417282 citations.
Topics: Population, Medicine, Cancer, Transplantation, Vitamin D and neurology
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University of Leicester1, National Institute for Health Research2, University of Oxford3, Wellcome Trust Centre for Human Genetics4, University of Cambridge5, Queen Mary University of London6, Technische Universität München7, Stanford University8, Icahn School of Medicine at Mount Sinai9, Imperial College Healthcare10, London North West Healthcare NHS Trust11, Imperial College London12, University of Dundee13, University of Leeds14, Massachusetts Institute of Technology15, Tartu University Hospital16, University of Ioannina17, Umeå University18, Harvard University19, Lund University20, Peking Union Medical College21, University College London22, University of Tampere23, Vanderbilt University24, Synlab Group25, Heidelberg University26, Medical University of Graz27, University of Ottawa28, University of Tartu29, Lebanese American University30, King Abdulaziz University31, Central Manchester University Hospitals NHS Foundation Trust32, University of Manchester33, National Institutes of Health34, St Bartholomew's Hospital35, Manchester Academic Health Science Centre36, Wellcome Trust Sanger Institute37, University of Lübeck38, Harokopio University39, Karolinska University Hospital40
TL;DR: This approach identified 13 new loci at genome-wide significance, 12 of which were on the previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals.
Abstract: Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10-8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; ncases = 10,801) as well as a stricter definition without angina (HARD; ncases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.
529 citations
Broad Institute1, Harvard University2, Washington University in St. Louis3, University of Copenhagen4, University of Milan5, University of Oxford6, University of North Carolina at Chapel Hill7, Fred Hutchinson Cancer Research Center8, University of Verona9, University of Ottawa10, University of Cambridge11, Memorial Hospital of South Bend12, University of Amsterdam13, University of Leicester14, Technische Universität München15, University of Lübeck16, Duke University17, University of Western Ontario18, Synlab Group19, Medical University of Graz20, Heidelberg University21, National Institutes of Health22, University of Pennsylvania23, University of Alabama at Birmingham24, University of Minnesota25, Wake Forest University26, Stanford University27, University of Mississippi28, Karolinska Institutet29, Merck & Co.30, University of Washington31, Group Health Cooperative32, University of Virginia33, University of Vermont34, Boston University35, University of Missouri–Kansas City36, University of Southern California37, Cleveland Clinic38, Ohio State University39, University of Texas Health Science Center at Houston40, University of Michigan41
TL;DR: Kathiresan et al. as mentioned in this paper used exome sequencing of nearly 10,000 people to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk.
Abstract: Exome sequence analysis of nearly 10,000 people was carried out to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk, identifying the key roles of low-density lipoprotein cholesterol and metabolism of triglyceride-rich lipoproteins. Sekar Kathiresan and colleagues use exome sequencing of nearly 10,000 people to probe the contribution of multiple rare mutations within a gene to risk for myocardial infarction at a population level. They find that mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) are associated with disease risk. When compared with non-carriers, LDLR mutation carriers had higher plasma levels of LDL cholesterol, whereas APOA5 mutation carriers had higher plasma levels of triglycerides. As well as confirming that APOA5 is a myocardial infarction gene, this work informs the design and conduct of rare-variant association studies for complex diseases. Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance1,2. When MI occurs early in life, genetic inheritance is a major component to risk1. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families3,4,5,6,7,8, whereas common variants at more than 45 loci have been associated with MI risk in the population9,10,11,12,13,14,15. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol16. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl−1. At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase15,17 and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.
521 citations
Karolinska Institutet1, University of Pisa2, University of Crete3, University College London4, University of Münster5, Dresden University of Technology6, University of Groningen7, University of Manchester8, McGill University9, University of Pécs10, University Medical Center Utrecht11, Charité12, University of Birmingham13, Medical University of Graz14, Université catholique de Louvain15, Istanbul University16, Copenhagen University Hospital17, Rio de Janeiro State University18, University of Paris-Sud19, University of Santo Tomas Hospital20, Medical University of Vienna21, VU University Amsterdam22, Odense University Hospital23, Moscow State University24, Hairmyres Hospital25, University of Düsseldorf26
TL;DR: Treating-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative and it is anticipated that ‘treating- to-target’ can and will be applicable to the care of patients with SLE.
Abstract: The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE.
521 citations
University of Cologne1, University of Genoa2, Post Graduate Institute of Medical Education and Research3, Westmead Hospital4, University of Sydney5, Federal University of São Paulo6, University of California, San Diego7, Medical University of Graz8, Innsbruck Medical University9, University of Lagos10, McGill University Health Centre11, Fudan University12, Radboud University Nijmegen13, University of Rennes14, Duke University15, University of Texas at Austin16, University of Texas Health Science Center at San Antonio17, Federal University of Paraná18, University of Texas Health Science Center at Houston19, Cardiff University20, Center for Infectious Disease Research and Policy21
TL;DR: It is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty, and recommended first-line therapy is either voriconazole or isavuconazole, while azole resistance is a concern.
Abstract: Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
519 citations
ETH Zurich1, Centre national de la recherche scientifique2, University of Évry Val d'Essonne3, Institut national de la recherche agronomique4, University of Guelph5, University College Cork6, University of Helsinki7, Wageningen University and Research Centre8, University of British Columbia9, University of Aberdeen10, Waseda University11, University of Tokyo12, Baylor College of Medicine13, Medical University of Graz14, University of Florida15, Okayama University16, Maastricht University17, Statens Serum Institut18, University of Western Ontario19, Shanghai Jiao Tong University20, King's College London21
TL;DR: A standardized DNA extraction method for human fecal samples is recommended, for which transferability across labs was established and which was further benchmarked using a mock community of known composition to improve comparability of human gut microbiome studies and facilitate meta-analyses.
Abstract: Technical variation in metagenomic analysis must be minimized to confidently assess the contributions of microbiota to human health. Here we tested 21 representative DNA extraction protocols on the same fecal samples and quantified differences in observed microbial community composition. We compared them with differences due to library preparation and sample storage, which we contrasted with observed biological variation within the same specimen or within an individual over time. We found that DNA extraction had the largest effect on the outcome of metagenomic analysis. To rank DNA extraction protocols, we considered resulting DNA quantity and quality, and we ascertained biases in estimates of community diversity and the ratio between Gram-positive and Gram-negative bacteria. We recommend a standardized DNA extraction method for human fecal samples, for which transferability across labs was established and which was further benchmarked using a mock community of known composition. Its adoption will improve comparability of human gut microbiome studies and facilitate meta-analyses.
516 citations
Authors
Showing all 5763 results
| Name | H-index | Papers | Citations |
|---|---|---|---|
| Ian J. Deary | 166 | 1795 | 114161 |
| James F. Wilson | 146 | 677 | 101883 |
| Nancy L. Pedersen | 145 | 890 | 94696 |
| William Wijns | 127 | 752 | 95517 |
| Andrew Simmons | 102 | 460 | 36608 |
| Franz Fazekas | 101 | 629 | 49775 |
| Hans-Peter Hartung | 100 | 810 | 49792 |
| Michael Trauner | 98 | 667 | 35543 |
| Dietmar Fuchs | 97 | 1119 | 39758 |
| Funda Meric-Bernstam | 96 | 753 | 36803 |
| Ulf Landmesser | 94 | 564 | 46096 |
| Aysegul A. Sahin | 93 | 322 | 30038 |
| Frank Madeo | 92 | 269 | 45942 |
| Takayoshi Ohkubo | 91 | 631 | 69634 |
| Jürgen C. Becker | 90 | 637 | 28741 |