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, Locus (genetics), Linkage disequilibrium
Papers published on a yearly basis
Papers
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TL;DR: This phylogeny makes sense of the shared characteristics of Xenoturbellida and Acoelomorpha, and implies the loss of various deuterostome characters in the Xenobiology including coelomic cavities, through gut and gill slits.
Abstract: Xenoturbellida and Acoelomorpha are marine worms with contentious ancestry. Both were originally associated with the flatworms (Platyhelminthes), but molecular data have revised their phylogenetic positions, generally linking Xenoturbellida to the deuterostomes and positioning the Acoelomorpha as the most basally branching bilaterian group(s). Recent phylogenomic data suggested that Xenoturbellida and Acoelomorpha are sister taxa and together constitute an early branch of Bilateria. Here we assemble three independent data sets-mitochondrial genes, a phylogenomic data set of 38,330 amino-acid positions and new microRNA (miRNA) complements-and show that the position of Acoelomorpha is strongly affected by a long-branch attraction (LBA) artefact. When we minimize LBA we find consistent support for a position of both acoelomorphs and Xenoturbella within the deuterostomes. The most likely phylogeny links Xenoturbella and Acoelomorpha in a clade we call Xenacoelomorpha. The Xenacoelomorpha is the sister group of the Ambulacraria (hemichordates and echinoderms). We show that analyses of miRNA complements have been affected by character loss in the acoels and that both groups possess one miRNA and the gene Rsb66 otherwise specific to deuterostomes. In addition, Xenoturbella shares one miRNA with the ambulacrarians, and two with the acoels. This phylogeny makes sense of the shared characteristics of Xenoturbellida and Acoelomorpha, such as ciliary ultrastructure and diffuse nervous system, and implies the loss of various deuterostome characters in the Xenacoelomorpha including coelomic cavities, through gut and gill slits.
399 citations
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TL;DR: A genetic-pleiotropy-informed method for improving gene discovery with the use of GWAS summary-statistics data and enrichment of SNPs associated with schizophrenia (SCZ) as a function of the association with several CVD risk factors and a corresponding reduction in false discovery rate is presented.
Abstract: Several lines of evidence suggest that genome-wide association studies (GWASs) have the potential to explain more of the "missing heritability" of common complex phenotypes. However, reliable methods for identifying a larger proportion of SNPs are currently lacking. Here, we present a genetic-pleiotropy-informed method for improving gene discovery with the use of GWAS summary-statistics data. We applied this methodology to identify additional loci associated with schizophrenia (SCZ), a highly heritable disorder with significant missing heritability. Epidemiological and clinical studies suggest comorbidity between SCZ and cardiovascular-disease (CVD) risk factors, including systolic blood pressure, triglycerides, low- and high-density lipoprotein, body mass index, waist-to-hip ratio, and type 2 diabetes. Using stratified quantile-quantile plots, we show enrichment of SNPs associated with SCZ as a function of the association with several CVD risk factors and a corresponding reduction in false discovery rate (FDR). We validate this "pleiotropic enrichment" by demonstrating increased replication rate across independent SCZ substudies. Applying the stratified FDR method, we identified 25 loci associated with SCZ at a conditional FDR level of 0.01. Of these, ten loci are associated with both SCZ and CVD risk factors, mainly triglycerides and low- and high-density lipoproteins but also waist-to-hip ratio, systolic blood pressure, and body mass index. Together, these findings suggest the feasibility of using genetic-pleiotropy-informed methods for improving gene discovery in SCZ and identifying potential mechanistic relationships with various CVD risk factors.
398 citations
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Beta1, Wellcome Trust Centre for Human Genetics2, Churchill Hospital3, University of California, San Diego4, French Institute of Health and Medical Research5, Columbia University6, John Radcliffe Hospital7, Central Manchester University Hospitals NHS Foundation Trust8, Life Technologies9, University of Lille Nord de France10, University of Virginia11, University of Barcelona12
TL;DR: A comprehensive strand-specific transcriptome map of human pancreatic islets and β cells is reported, and a new class of islet-cell genes relevant to β cell programming and diabetes pathophysiology are revealed.
397 citations
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TL;DR: The discovery of this remarkable new photoreceptor system is outlined, the structure of melanopsin is reviewed, and a working model of melanOPSin phototransduction is concluded.
395 citations
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TL;DR: The results implicate a previously unrecognized pathway for the development of common allergic illnesses and found that a Glu420→Lys variant shows significant association with atopy and AD in two independent panels of families.
Abstract: Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions1, including the chromosome 5q31 cytokine cluster2,3,4. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment5. The gene underlying Netherton disease (SPINK5)6 encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus6,7. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420→Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses.
391 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 |