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
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TL;DR: The DRD4 gene may be associated with measures of novelty seeking and impulsivity but not extraversion, and the association of the C-521T variant with these measures, if genuine, may account for up to 3% of phenotypic variance.
390 citations
Swiss Institute of Bioinformatics1, University of Copenhagen2, University of Bern3, Griffith University4, Pompeu Fabra University5, Instituto Gulbenkian de Ciência6, Wellcome Trust Sanger Institute7, Aarhus University8, University of California, Berkeley9, Max Planck Society10, Technical University of Denmark11, University of Cambridge12, King Abdullah University of Science and Technology13, ETH Zurich14, Monash University Malaysia Campus15, Centre national de la recherche scientifique16, University of Porto17, University College London18, Papua New Guinea Institute of Medical Research19, University of Papua New Guinea20, University of Otago21, Wellcome Trust Centre for Human Genetics22, Estonian Biocentre23, University of Oxford24, University of Western Australia25, Yale University26, University of California, San Francisco27
TL;DR: A population expansion in northeast Australia during the Holocene epoch associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama–Nyungan languages is inferred.
Abstract: The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama–Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25–40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all of the studied Aboriginal Australians descend from a single founding population that differentiated ~10–32 kya. We infer a population expansion in northeast Australia during the Holocene epoch (past 10,000 years) associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama–Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51–72 kya, following a single out-of-Africa dispersal, and subsequently admixed with archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.
389 citations
TL;DR: Investigation of the entire coding region of FOXP2, including alternatively spliced exons, in 49 probands affected with verbal dyspraxia and the discovery of the first nonsense mutation in FoxP2 opens the door for detailed investigations of neurodevelopment in people carrying different etiological variants of the gene.
Abstract: FOXP2, the first gene to have been implicated in a developmental communication disorder, offers a unique entry point into neuromolecular mechanisms influencing human speech and language acquisition. In multiple members of the well-studied KE family, a heterozygous missense mutation in FOXP2 causes problems in sequencing muscle movements required for articulating speech (developmental verbal dyspraxia), accompanied by wider deficits in linguistic and grammatical processing. Chromosomal rearrangements involving this locus have also been identified. Analyses of FOXP2 coding sequence in typical forms of specific language impairment (SLI), autism, and dyslexia have not uncovered any etiological variants. However, no previous study has performed mutation screening of children with a primary diagnosis of verbal dyspraxia, the most overt feature of the disorder in affected members of the KE family. Here, we report investigations of the entire coding region of FOXP2, including alternatively spliced exons, in 49 probands affected with verbal dyspraxia. We detected variants that alter FOXP2 protein sequence in three probands. One such variant is a heterozygous nonsense mutation that yields a dramatically truncated protein product and cosegregates with speech and language difficulties in the proband, his affected sibling, and their mother. Our discovery of the first nonsense mutation in FOXP2 now opens the door for detailed investigations of neurodevelopment in people carrying different etiological variants of the gene. This endeavor will be crucial for gaining insight into the role of FOXP2 in human cognition.
387 citations
Medical Research Council1, Wellcome Trust Sanger Institute2, Wellcome Trust Centre for Human Genetics3, University of Oxford4, Malawi-Liverpool-Wellcome Trust Clinical Research Programme5, University of Buea6, Kwame Nkrumah University of Science and Technology7, Papua New Guinea Institute of Medical Research8, University of Ibadan9, National Institute for Biological Standards and Control10, University of Bamako11, University of London12, University College London13, Bernhard Nocht Institute for Tropical Medicine14, University of Colombo15, University of Khartoum16, Wellcome Trust17, University of Ghana18, National Institute for Medical Research19, Muhimbili University of Health and Allied Sciences20, Sapienza University of Rome21, University of Malawi22, University of Maryland, Baltimore23, Pasteur Institute24, Mahidol University25, Michigan State University26, Stockholm University27
TL;DR: These findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
Abstract: We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
384 citations
Imperial College London1, Agency for Science, Technology and Research2, University of Oulu3, Wellcome Trust Centre for Human Genetics4, University of Milan5, University of Bristol6, National Institutes of Health7, Ealing Hospital8, university of lille9, Pasteur Institute of Lille10, Hammersmith Hospital11, Baker IDI Heart and Diabetes Institute12, National University of Singapore13, French Institute of Health and Medical Research14, Technische Universität München15, University of Kiel16, University of Oxford17, University of Cambridge18, University of Surrey19, Hannover Medical School20, Max Healthcare21, University of Kelaniya22, University of Mauritius23, University of Helsinki24, Imperial College Healthcare25, University of Pennsylvania26, University of Eastern Finland27, University of Düsseldorf28, Dresden University of Technology29, National Institute for Health Research30
TL;DR: A nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population study.
384 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 |