Institution
University of Liverpool
Education•Liverpool, United Kingdom•
About: University of Liverpool is a education organization based out in Liverpool, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 40406 authors who have published 94388 publications receiving 3188970 citations. The organization is also known as: Liverpool University & The University of Liverpool.
Papers published on a yearly basis
Papers
More filters
••
TL;DR: This article identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height, and all common variants together captured 60% of heritability.
Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
1,872 citations
••
TL;DR: This article conducted a meta-analysis of coronary artery disease (CAD) cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 millions low-frequency (0.005 < MAF < 0.5) variants.
Abstract: Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
1,839 citations
••
TL;DR: A panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis as discussed by the authors.
Abstract: DNA damage checkpoint genes, such as p53, are frequently mutated in human cancer, but the selective pressure for their inactivation remains elusive. We analysed a panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis. Progression to carcinoma was associated with p53 or 53BP1 inactivation and decreased apoptosis. A DNA damage response was also observed in dysplastic nevi and in human skin xenografts, in which hyperplasia was induced by overexpression of growth factors. Both lung and experimentally-induced skin hyperplasias showed allelic imbalance at loci that are prone to DNA double-strand break formation when DNA replication is compromised (common fragile sites). We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations.
1,829 citations
••
Wellcome Trust Sanger Institute1, University Medical Center Groningen2, Harvard University3, The Chinese University of Hong Kong4, Wellcome Trust Centre for Human Genetics5, Yonsei University6, Icahn School of Medicine at Mount Sinai7, University of Delhi8, University of Liverpool9, Central Manchester University Hospitals NHS Foundation Trust10, St Mary's Hospital11, Asan Medical Center12
TL;DR: The first trans-ancestry association study of IBD is reported, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent, implicate 38 loci in IBD risk for the first time.
Abstract: Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.
1,826 citations
••
TL;DR: SGLT2i have moderate benefits on atherosclerotic major adverse cardiovascular events that seem confined to patients with established atheroscerotic cardiovascular disease, however, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease regardless of existing atherosclerosis or a history of heart failure.
1,797 citations
Authors
Showing all 40921 results
Name | H-index | Papers | Citations |
---|---|---|---|
Lei Jiang | 170 | 2244 | 135205 |
Gregory Y.H. Lip | 169 | 3159 | 171742 |
Ian J. Deary | 166 | 1795 | 114161 |
Nicholas J. White | 161 | 1352 | 104539 |
Tomas Hökfelt | 158 | 1033 | 95979 |
William J. Sutherland | 148 | 966 | 94423 |
Tommaso Dorigo | 141 | 1806 | 104276 |
Paul Jackson | 141 | 1372 | 93464 |
Andrew Askew | 140 | 1496 | 99635 |
Stephen Wimpenny | 138 | 1489 | 104084 |
Robin Erbacher | 138 | 1721 | 100252 |
Andrew Mehta | 137 | 1444 | 101810 |
Tim Jones | 135 | 1314 | 91422 |
Christophe Delaere | 135 | 1320 | 96742 |
Sinead Farrington | 133 | 1422 | 91099 |