Institution
University of Exeter
Education•Exeter, United Kingdom•
About: University of Exeter is a education organization based out in Exeter, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 15820 authors who have published 50650 publications receiving 1793046 citations. The organization is also known as: Exeter University & University of the South West of England.
Papers published on a yearly basis
Papers
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TL;DR: This work states that genome association studies are central to efforts to identify and characterise genomic variants underlying susceptibility to multifactorial disease, and that study quality, rather than significance value, needs to play the dominant part.
501 citations
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501 citations
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Georgia Institute of Technology1, Leipzig University2, Johns Hopkins University3, University of Cambridge4, University of Tartu5, Ontario Institute for Cancer Research6, University of Washington7, VU University Amsterdam8, University of Chicago9, Greifswald University Hospital10, University of Bristol11, Erasmus University Rotterdam12, University of Exeter13, University of Lausanne14, Swiss Institute of Bioinformatics15, University of Geneva16, University of Helsinki17, Weizmann Institute of Science18, Agency for Science, Technology and Research19, University of Queensland20, Leiden University Medical Center21, University of Liège22, University of Oxford23, University of Tampere24, Stanford University25, Turku University Hospital26, Maastricht University Medical Centre27, Karolinska Institutet28, Radboud University Nijmegen29, Utrecht University30, European Bioinformatics Institute31
TL;DR: It is observed that cis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting the ability to use cis- eZTLs to pinpoint causal genes within susceptibility loci.
Abstract: While many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear. To identify these effects, we performed cis- and trans-expression quantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium. We observed that cis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting our ability to use cis-eQTLs to pinpoint causal genes within susceptibility loci. In contrast, trans-eQTLs (detected for 37% of 10,317 studied trait-associated variants) were more informative. Multiple unlinked variants, associated to the same complex trait, often converged on trans-genes that are known to play central roles in disease etiology. We observed the same when ascertaining the effect of polygenic scores calculated for 1,263 genome-wide association study (GWAS) traits. Expression levels of 13% of the studied genes correlated with polygenic scores, and many resulting genes are known to drive these traits.
500 citations
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499 citations
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TL;DR: In this article, the authors used genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies and found robust evidence for 123 signals at 106 genomic loci associated with age at menarche.
Abstract: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
498 citations
Authors
Showing all 16338 results
Name | H-index | Papers | Citations |
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Frank B. Hu | 250 | 1675 | 253464 |
John C. Morris | 183 | 1441 | 168413 |
David W. Johnson | 160 | 2714 | 140778 |
Kevin J. Gaston | 150 | 750 | 85635 |
Andrew T. Hattersley | 146 | 768 | 106949 |
Timothy M. Frayling | 133 | 500 | 100344 |
Joel N. Hirschhorn | 133 | 431 | 101061 |
Jonathan D. G. Jones | 129 | 417 | 80908 |
Graeme I. Bell | 127 | 531 | 61011 |
Mark D. Griffiths | 124 | 1238 | 61335 |
Tao Zhang | 123 | 2772 | 83866 |
Brinick Simmons | 122 | 691 | 69350 |
Edzard Ernst | 120 | 1326 | 55266 |
Michael Stumvoll | 119 | 655 | 69891 |
Peter McGuffin | 117 | 624 | 62968 |