Institution
Charité
Healthcare•Berlin, Germany•
About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.
Topics: Population, Transplantation, Medicine, Cancer, Immune system
Papers published on a yearly basis
Papers
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Elizabeth K. Speliotes1, Elizabeth K. Speliotes2, Cristen J. Willer3, Sonja I. Berndt +410 more•Institutions (86)
TL;DR: Genetic loci associated with body mass index map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor, which may provide new insights into human body weight regulation.
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
2,632 citations
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TL;DR: MutationTaster allows the efficient filtering of NGS data for alterations with high disease-causing potential and provides Perl scripts that can process data from all major platforms (Roche 454, Illumina Genome Analyzer and ABI SOLiD).
Abstract: (simple_aae) or at alterations causing complex changes in the amino acid sequence (complex_aae). To train the classifier, we generated a dataset with all available and suitable common polymorphisms and known diseasecausing mutations extracted from common databases and the literature. We cross-validated the classifier five times including all three prediction models and obtained an overall accuracy of 91.1 ± 0.1%. We also compared MutationTaster with similar applications (Panther3, Pmut4, PolyPhen and PolyPhen-2 (ref. 5) and ‘screening for non-acceptable polymorphisms’ (SNAP)6) and analyzed the identical 1,000 disease-linked mutations and 1,000 polymorphisms with all programs. For this comparison, we used only alterations causing single amino acid exchanges. MutationTaster performed best in terms of accuracy and speed (Table 1). A description of all training and validation procedures and detailed statistics are available in Supplementary Methods. MutationTaster can be used via an intuitive web interface to analyze single mutations as well as in batch mode. To streamline and to standardize the analysis of NGS data, we provide Perl scripts that can process data from all major platforms (Roche 454, Illumina Genome Analyzer and ABI SOLiD). MutationTaster hence allows the efficient filtering of NGS data for alterations with high disease-causing potential (see Supplementary Methods for an example). Present limitations of the software comprise its inability to analyze insertion-deletions greater than 12 base pairs and alterations spanning an intron-exon border. Also, analysis of non-exonic alterations is restricted to Kozak consensus sequence, splice sites and poly(A) signal. We will add tests for other sequence motifs in the near future. MutationTaster is available at http://www.mutationtaster.org/.
2,628 citations
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VU University Medical Center1, Charité2, Keele University3, University of Erlangen-Nuremberg4, Katholieke Universiteit Leuven5, University of Eastern Piedmont6, Oslo University Hospital7, University of Porto8, University of Debrecen9, Maastricht University10, University of Göttingen11, Stavanger University Hospital12, Cardiff University13
TL;DR: The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies forHFNEF.
Abstract: Diastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated. The diagnosis of HFNEF requires the following conditions to be satisfied: (i) signs or symptoms of heart failure; (ii) normal or mildly abnormal systolic LV function; (iii) evidence of diastolic LV dysfunction. Normal or mildly abnormal systolic LV function implies both an LVEF > 50% and an LV end-diastolic volume index (LVEDVI) 16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E' > 15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15 > E/E' > 8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation. A similar strategy with focus on a high negative predictive value of successive investigations is proposed for the exclusion of HFNEF in patients with breathlessness and no signs of congestion. The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies for HFNEF.
2,578 citations
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Stephen Sawcer1, Garrett Hellenthal2, Matti Pirinen2, Chris C. A. Spencer2 +262 more•Institutions (67)
TL;DR: In this article, a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, they have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci.
Abstract: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
2,511 citations
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University of Kiel1, Cedars-Sinai Medical Center2, Wellcome Trust Sanger Institute3, University of Pennsylvania4, QIMR Berghofer Medical Research Institute5, Peninsula College of Medicine and Dentistry6, University of Edinburgh7, University of Cambridge8, University of Otago9, University of Washington10, University of Groningen11, University of Liège12, Harvard University13, Casa Sollievo della Sofferenza14, King's College London15, University of Chicago16, Yale University17, Johns Hopkins University18, Ludwig Maximilian University of Munich19, Charité20, McGill University21, Lille University of Science and Technology22, Cincinnati Children's Hospital Medical Center23, Ghent University24, Torbay Hospital25, Mater Health Services26, Université libre de Bruxelles27, RWTH Aachen University28, University of Utah29, Örebro University30, Leiden University31, University of Paris32, Technion – Israel Institute of Technology33, University of Western Australia34, Tel Aviv University35, University of Dundee36, University of Manchester37, University of Pittsburgh38, Royal Hospital for Sick Children39, Katholieke Universiteit Leuven40, Guy's and St Thomas' NHS Foundation Trust41, University of Bern42, University of Toronto43, University of Amsterdam44, Karolinska Institutet45, University of Zurich46, Université de Montréal47, Emory University48, Newcastle University49
TL;DR: A meta-analysis of six Crohn's disease genome-wide association studies and a series of in silico analyses highlighted particular genes within these loci implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.
Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
2,482 citations
Authors
Showing all 30787 results
Name | H-index | Papers | Citations |
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JoAnn E. Manson | 270 | 1819 | 258509 |
Yi Chen | 217 | 4342 | 293080 |
David J. Hunter | 213 | 1836 | 207050 |
Raymond J. Dolan | 196 | 919 | 138540 |
John P. A. Ioannidis | 185 | 1311 | 193612 |
Stefan Schreiber | 178 | 1233 | 138528 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Eric J. Nestler | 178 | 748 | 116947 |
Klaus Rajewsky | 154 | 504 | 88793 |
Charles B. Nemeroff | 149 | 979 | 90426 |
Andreas Pfeiffer | 149 | 1756 | 131080 |
Rinaldo Bellomo | 147 | 1714 | 120052 |
Jean Bousquet | 145 | 1288 | 96769 |
Christopher Hill | 144 | 1562 | 128098 |
Holger J. Schünemann | 141 | 810 | 113169 |