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: Dengue virus (DENV) modifies ER membrane structure to promote replication and efficient encapsidation of the genome into progeny virus, which could explain the coordination of distinct steps of the flavivirus replication cycle.
915 citations
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UCL Institute of Child Health1, University of Helsinki2, National Institutes of Health3, VU University Amsterdam4, University of Graz5, Harvard University6, University of Cambridge7, McGill University8, Wake Forest University9, Peninsula College of Medicine and Dentistry10, University of Gothenburg11, University of Zagreb12, University of Edinburgh13, University of Maryland, Baltimore14, University of Oxford15, Wellcome Trust Centre for Human Genetics16, Churchill Hospital17, University of Oulu18, Heidelberg University19, Uppsala University20, Western General Hospital21, King's College London22, Wellcome Trust Sanger Institute23, NHS Blood and Transplant24, University of Southampton25, University of London26, GlaxoSmithKline27, University College London28
TL;DR: A mendelian randomization study based on data from multiple cohorts conducted by Karani Santhanakrishnan Vimaleswaran and colleagues re-examines the causal nature of the relationship between vitamin D levels and obesity.
Abstract: BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.
851 citations
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TL;DR: The substantial increase in the female to male sex ratio in Canada seems to result from a disproportional increase in incidence of multiple sclerosis in women, which implies that a large proportion of several sclerosis cases may be preventable in situ.
Abstract: Summary Background Incidence of multiple sclerosis is thought to be increasing, but this notion has been difficult to substantiate. In a longitudinal population-based dataset of patients with multiple sclerosis obtained over more than three decades, we did not show a difference in time to diagnosis by sex. We reasoned that if a sex-specific change in incidence was occurring, the female to male sex ratio would serve as a surrogate of incidence change. Methods Since environmental risk factors seem to act early in life, we calculated sex ratios by birth year in 27 074 Canadian patients with multiple sclerosis identified as part of a longitudinal population-based dataset. Findings The female to male sex ratio by year of birth has been increasing for at least 50 years and now exceeds 3·2:1 in Canada. Year of birth was a significant predictor for sex ratio (p 2 =124·4; rank correlation r =0·84). Interpretation The substantial increase in the female to male sex ratio in Canada seems to result from a disproportional increase in incidence of multiple sclerosis in women. This rapid change must have environmental origins even if it is associated with a gene–environment interaction, and implies that a large proportion of multiple sclerosis cases may be preventable in situ. Although the reasons why incidence of the disease is increasing are unknown, there are major implications for health-care provision because lifetime costs of multiple sclerosis exceed £1 million per case in the UK.
842 citations
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University of Exeter1, Wellcome Trust Centre for Human Genetics2, University of Oxford3, Queen Mary University of London4, University of Bristol5, University of Leicester6, University of Leeds7, British Heart Foundation8, University Hospital of Lausanne9, Swiss Institute of Bioinformatics10, University of Lausanne11, GlaxoSmithKline12, University of Cambridge13, National Health Service14, University of Dundee15, Imperial College London16, Wellcome Trust Sanger Institute17
TL;DR: The loci the authors identified implicate genes in Hedgehog signaling, extracellular matrix, and cancer pathways, and provide new insights into human growth and developmental processes and insights into the genetic architecture of a classic quantitative trait.
Abstract: Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.
828 citations
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TL;DR: The implementation of the statistical total correlation spectroscopy (STOCSY) analysis method with supervised pattern recognition and particularly orthogonal projection on latent structure-discriminant analysis (O-PLS-DA) offers a new powerful framework for analysis of metabonomic data.
Abstract: We describe here the implementation of the statistical total correlation spectroscopy (STOCSY) analysis method for aiding the identification of potential biomarker molecules in metabonomic studies based on NMR spectroscopic data. STOCSY takes advantage of the multicollinearity of the intensity variables in a set of spectra (in this case 1H NMR spectra) to generate a pseudo-two-dimensional NMR spectrum that displays the correlation among the intensities of the various peaks across the whole sample. This method is not limited to the usual connectivities that are deducible from more standard two-dimensional NMR spectroscopic methods, such as TOCSY. Moreover, two or more molecules involved in the same pathway can also present high intermolecular correlations because of biological covariance or can even be anticorrelated. This combination of STOCSY with supervised pattern recognition and particularly orthogonal projection on latent structure−discriminant analysis (O-PLS-DA) offers a new powerful framework for ...
823 citations
Authors
Showing all 2127 results
Name | H-index | Papers | Citations |
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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 |