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Institution

Wellcome Trust Centre for Human Genetics

FacilityOxford, 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.


Papers
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Journal ArticleDOI
TL;DR: This study shows an association between IL23R and all subphenotypes of CD with a smaller effect on UC, providing clear evidence that genome-wide association scanning can successfully identify true complex disease genes.

191 citations

Journal ArticleDOI
TL;DR: A genome-wide association study using data from UK Biobank identifies loci for knee- and hip-specific disease and establishes causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.
Abstract: Osteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. We established causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.

191 citations

Journal ArticleDOI
01 Sep 2004-Genomics
TL;DR: Protein sequence comparisons suggest that intramolecular duplications have played an important role in the evolution of this gene family and three new genes encoding these CHAC-similar proteins are characterized.

190 citations

Journal ArticleDOI
Haoyu Zhang1, Haoyu Zhang2, Thomas U. Ahearn2, Julie Lecarpentier3  +299 moreInstitutions (123)
TL;DR: A genome-wide association study including 133,384 breast cancer cases and 113,789 controls plus 18,908 BRCA1 mutation carriers of European ancestry provides an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

190 citations

Journal ArticleDOI
TL;DR: Five polymorphic non-HLA host genetic factors that might influence susceptibility to DHF were assessed and the less frequent t allele of a variant at position 352 of the vitamin D receptor (VDR) gene was associated with resistance to severe dengue.
Abstract: Dengue is an increasingly important cause of morbidity and mortality in the tropics, with more than a billion people at risk each year. Immunologic enhancement is thought to contribute to disease pathogenesis. Only a very small proportion of infected individuals develop life-threatening dengue hemorrhagic fever (DHF). In a large case-control study with 400 DHF patients and 300 matched controls, we have assessed five polymorphic non-HLA host genetic factors that might influence susceptibility to DHF. The less frequent t allele of a variant at position 352 of the vitamin D receptor (VDR) gene was associated with resistance to severe dengue (P = 0.03). Homozygotes for the arginine variant at position 131 of the Fc gammaRIIA gene, who have less capacity to opsonize IgG2 antibodies, may also be protected from DHF (one-tailed P = 0.03). No associations were found with polymorphisms in the mannose binding lectin, interleukin-1 (IL-4), and IL-1 receptor antagonist genes. Further studies to confirm these associations are warranted.

190 citations


Authors

Showing all 2127 results

NameH-indexPapersCitations
Mark I. McCarthy2001028187898
John P. A. Ioannidis1851311193612
Gonçalo R. Abecasis179595230323
Simon I. Hay165557153307
Robert Plomin151110488588
Ashok Kumar1515654164086
Julian Parkhill149759104736
James F. Wilson146677101883
Jeremy K. Nicholson14177380275
Hugh Watkins12852491317
Erik Ingelsson12453885407
Claudia Langenberg12445267326
Adrian V. S. Hill12258964613
John A. Todd12151567413
Elaine Holmes11956058975
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202221
202183
202074
2019134
2018182
2017323