Institution
Medical Research Council
Government•London, United Kingdom•
About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.
Papers published on a yearly basis
Papers
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TL;DR: A genome-wide means of mapping protein–RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP), which revealed a large number of Nova–RNA interactions in 3′ untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain.
Abstract: Protein-RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.
1,313 citations
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Royal Edinburgh Hospital1, Centre for Mental Health2, King's College London3, University of Glasgow4, University of Edinburgh5, Medical Research Council6, University of Münster7, University of Melbourne8, University of Freiburg9, University of Queensland10, Broad Institute11, Harvard University12, Charité13, Karolinska Institutet14, University of North Carolina at Chapel Hill15
TL;DR: A genetic meta-analysis of depression found 269 associated genes that highlight several potential drug repositioning opportunities, and relationships with depression were found for neuroticism and smoking.
Abstract: Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.
1,312 citations
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TL;DR: In this paper, the authors report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirm the previously reported association of AITD with TSHR and FCRL3.
Abstract: We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
1,299 citations
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TL;DR: Results from this randomised trial provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer.
1,296 citations
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TL;DR: Age-related decline in vascular health is associated with progressive endothelial dysfunction in normal humans, and this appears to occur earlier in men than in women, but in women a steep decline commences at around the time of the menopause, consistent with a protective effect of estrogens on the arterial wall.
1,291 citations
Authors
Showing all 16441 results
Name | H-index | Papers | Citations |
---|---|---|---|
Shizuo Akira | 261 | 1308 | 320561 |
Trevor W. Robbins | 231 | 1137 | 164437 |
Richard A. Flavell | 231 | 1328 | 205119 |
George Davey Smith | 224 | 2540 | 248373 |
Nicholas J. Wareham | 212 | 1657 | 204896 |
Cyrus Cooper | 204 | 1869 | 206782 |
Martin White | 196 | 2038 | 232387 |
Frank E. Speizer | 193 | 636 | 135891 |
Michael Rutter | 188 | 676 | 151592 |
Richard Peto | 183 | 683 | 231434 |
Terrie E. Moffitt | 182 | 594 | 150609 |
Kay-Tee Khaw | 174 | 1389 | 138782 |
Chris D. Frith | 173 | 524 | 130472 |
Phillip A. Sharp | 172 | 614 | 117126 |
Avshalom Caspi | 170 | 524 | 113583 |