Institution
Wellcome Trust Centre for Human Genetics
Facility•Oxford, United Kingdom•
About: Wellcome Trust Centre for Human Genetics is a facility organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 2122 authors who have published 4269 publications receiving 433899 citations.
Topics: Population, Genome-wide association study, Single-nucleotide polymorphism, Gene, Locus (genetics)
Papers published on a yearly basis
Papers
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TL;DR: This work has identified a gene in the CHAC critical region and found 16 different mutations in individuals with chorea-acanthocytosis, which encodes an evolutionarily conserved protein that is probably involved in protein sorting.
Abstract: Chorea-acanthocytosis (CHAC, MIM 200150) is an autosomal recessive neurodegenerative disorder characterized by the gradual onset of hyperkinetic movements and abnormal erythrocyte morphology (acanthocytosis). Neurological findings closely resemble those observed in Huntington disease. We identified a gene in the CHAC critical region and found 16 different mutations in individuals with chorea-acanthocytosis. CHAC encodes an evolutionarily conserved protein that is probably involved in protein sorting.
302 citations
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TL;DR: A common theme of generalized epidermal dysfunction manifesting as a compromised skin barrier and failure to protect against, or aberrant responses to, microbial insults and antigens is suggested.
Abstract: Atopic dermatitis (AD) is a chronic itching (pruritic) skin disease. It results from a complex interplay between strong genetic and environmental factors. Genome screens of families with AD have implicated chromosomal regions that overlap with other skin diseases and with inflammatory and autoimmune diseases. These, together with candidate gene studies, provide novel insights into the pathogenesis of AD. The findings suggest a common theme of generalized epidermal dysfunction manifesting as a compromised skin barrier and failure to protect against, or aberrant responses to, microbial insults and antigens. Recent genetic advances with high-throughput methods for gene identification, such as DNA microarrays and whole-genome genotyping, will help further dissect this complex trait. This will aid disease-defining criteria and focused therapies for AD.
302 citations
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Alexander Fleming Biomedical Sciences Research Center1, Wellcome Trust Centre for Human Genetics2, Medical Research Council3, Stanford University4, Harvard University5, University of Ferrara6, Boston University7, University of Michigan8, Science for Life Laboratory9, Charité10, Steno Diabetes Center11, University of Copenhagen12, Icahn School of Medicine at Mount Sinai13, University of California, Los Angeles14, Pasteur Institute15, National Institute for Health Research16, National Institutes of Health17, Leipzig University18, Wellcome Trust Sanger Institute19, University of Eastern Finland20, Imperial College London21, McMaster University22, University of Tübingen23, University of Gothenburg24, University of Southern California25, University of North Carolina at Chapel Hill26, Uppsala University Hospital27, University of Southern Denmark28, Newcastle University29
TL;DR: By assembling extensive data on continuous glycemic traits, this work has exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
Abstract: Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
298 citations
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TL;DR: In this article, the authors investigated whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer.
298 citations
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Imperial College London1, University of Missouri2, University of Glasgow3, European Bioinformatics Institute4, Wellcome Trust Centre for Human Genetics5, Medical College of Wisconsin6, University of Wisconsin-Madison7, Mayo Clinic8, Karolinska Institutet9, Max Delbrück Center for Molecular Medicine10, Kyoto University11, University of Iowa12, University of Edinburgh13, Charles University in Prague14, Academy of Sciences of the Czech Republic15, University of Nebraska Medical Center16, Université libre de Bruxelles17, Baylor College of Medicine18
TL;DR: This work outlines achievements in rat gene discovery to date, shows how these findings have been translated to human disease, and document an increasing pace of discovery of new disease genes, pathways and mechanisms.
Abstract: The rat is an important system for modeling human disease. Four years ago, the rich 150-year history of rat research was transformed by the sequencing of the rat genome, ushering in an era of exceptional opportunity for identifying genes and pathways underlying disease phenotypes. Genome-wide association studies in human populations have recently provided a direct approach for finding robust genetic associations in common diseases, but identifying the precise genes and their mechanisms of action remains problematic. In the context of significant progress in rat genomic resources over the past decade, we outline achievements in rat gene discovery to date, show how these findings have been translated to human disease, and document an increasing pace of discovery of new disease genes, pathways and mechanisms. Finally, we present a set of principles that justify continuing and strengthening genetic studies in the rat model, and further development of genomic infrastructure for rat research.
296 citations
Authors
Showing all 2127 results
Name | H-index | Papers | Citations |
---|---|---|---|
Mark I. McCarthy | 200 | 1028 | 187898 |
John P. A. Ioannidis | 185 | 1311 | 193612 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
Simon I. Hay | 165 | 557 | 153307 |
Robert Plomin | 151 | 1104 | 88588 |
Ashok Kumar | 151 | 5654 | 164086 |
Julian Parkhill | 149 | 759 | 104736 |
James F. Wilson | 146 | 677 | 101883 |
Jeremy K. Nicholson | 141 | 773 | 80275 |
Hugh Watkins | 128 | 524 | 91317 |
Erik Ingelsson | 124 | 538 | 85407 |
Claudia Langenberg | 124 | 452 | 67326 |
Adrian V. S. Hill | 122 | 589 | 64613 |
John A. Todd | 121 | 515 | 67413 |
Elaine Holmes | 119 | 560 | 58975 |