Institution
Wellcome Trust Sanger Institute
Nonprofit•Cambridge, United Kingdom•
About: Wellcome Trust Sanger Institute is a nonprofit organization based out in Cambridge, United Kingdom. It is known for research contribution in the topics: Population & Genome. The organization has 4009 authors who have published 9671 publications receiving 1224479 citations.
Topics: Population, Genome, Gene, Genome-wide association study, Genomics
Papers published on a yearly basis
Papers
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TL;DR: ANGPTL3 deficiency is associated with protection from CAD, and individuals in the lowest tertile of circulating ANGPTL 3 concentrations, compared with the highest, had reduced odds of MI.
286 citations
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VU University Amsterdam1, University of Twente2, QIMR Berghofer Medical Research Institute3, University of Minnesota4, University of Edinburgh5, Radboud University Nijmegen6, University of Illinois at Urbana–Champaign7, University of Tartu8, Erasmus University Rotterdam9, University of Chicago10, Martin Luther University of Halle-Wittenberg11, University of Helsinki12, Virginia Commonwealth University13, National Research Council14, National Institutes of Health15, University of Greifswald16, Karolinska Institutet17, University of Michigan18, Washington University in St. Louis19, Estonian Academy of Sciences20, Duke University21, University of Bristol22, Princeton University23, University of Queensland24, National Institute for Health and Welfare25, University of Brescia26, Western General Hospital27, Wellcome Trust Sanger Institute28, University of Split29, University of Turku30, Indiana University31, University of Missouri32, Florida State University33, Trinity College, Dublin34, University of Southern Denmark35
TL;DR: This study identifies a novel locus for neuroticism located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies and shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants.
Abstract: Importance Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases).
Objectives To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.
Design, Setting, and Participants Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.
Main Outcomes and Measures Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.
Results A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10−9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10−8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10−12 < P < .05) and MDD (4.02 × 10−9 < P < .05) in the 2 other cohorts.
Conclusions and Relevance This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism
286 citations
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National University of General San Martín1, Wellcome Trust Sanger Institute2, University of Washington3, Marine Biological Laboratory4, Pfizer5, University of Pennsylvania6, University of Melbourne7, University of Dundee8, Brandeis University9, World Health Organization10, University of California, San Francisco11
TL;DR: The development of the TDR Targets database is discussed, which encompasses extensive genetic, biochemical and pharmacological data related to tropical disease pathogens, as well as computationally predicted druggability for potential targets and compound desirability information, and aims to facilitate the identification and prioritization of candidate drug targets for pathogens.
Abstract: The increasing availability of genomic data for pathogens that cause tropical diseases has created new opportunities for drug discovery and development. However, if the potential of such data is to be fully exploited, the data must be effectively integrated and be easy to interrogate. Here, we discuss the development of the TDR Targets database (http://tdrtargets.org), which encompasses extensive genetic, biochemical and pharmacological data related to tropical disease pathogens, as well as computationally predicted druggability for potential targets and compound desirability information. By allowing the integration and weighting of this information, this database aims to facilitate the identification and prioritization of candidate drug targets for pathogens.
286 citations
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TL;DR: The trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry finds genetic variants at 12 new loci to be associated with blood pressure, providing new evidence for the role of DNA methylation in blood pressure regulation.
Abstract: We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
286 citations
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TL;DR: To identify novel DD-associated genes, healthcare and research exome sequences are integrated on 31,058 DD parent-offspring trios, and a simulation-based statistical test is developed to identify gene-specific enrichments of DNMs.
Abstract: De novo mutations in protein-coding genes are a well-established cause of developmental disorders1. However, genes known to be associated with developmental disorders account for only a minority of the observed excess of such de novo mutations1,2. Here, to identify previously undescribed genes associated with developmental disorders, we integrate healthcare and research exome-sequence data from 31,058 parent-offspring trios of individuals with developmental disorders, and develop a simulation-based statistical test to identify gene-specific enrichment of de novo mutations. We identified 285 genes that were significantly associated with developmental disorders, including 28 that had not previously been robustly associated with developmental disorders. Although we detected more genes associated with developmental disorders, much of the excess of de novo mutations in protein-coding genes remains unaccounted for. Modelling suggests that more than 1,000 genes associated with developmental disorders have not yet been described, many of which are likely to be less penetrant than the currently known genes. Research access to clinical diagnostic datasets will be critical for completing the map of genes associated with developmental disorders.
286 citations
Authors
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Name | H-index | Papers | Citations |
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Nicholas J. Wareham | 212 | 1657 | 204896 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
Panos Deloukas | 162 | 410 | 154018 |
Michael R. Stratton | 161 | 443 | 142586 |
David W. Johnson | 160 | 2714 | 140778 |
Michael John Owen | 160 | 1110 | 135795 |
Naveed Sattar | 155 | 1326 | 116368 |
Robert E. W. Hancock | 152 | 775 | 88481 |
Julian Parkhill | 149 | 759 | 104736 |
Nilesh J. Samani | 149 | 779 | 113545 |
Michael Conlon O'Donovan | 142 | 736 | 118857 |
Jian Yang | 142 | 1818 | 111166 |
Christof Koch | 141 | 712 | 105221 |
Andrew G. Clark | 140 | 823 | 123333 |
Stylianos E. Antonarakis | 138 | 746 | 93605 |