11 research outputs found
Genetic variation in PLEKHG1 is associated with white matter hyperintensities (n = 11,226).
OBJECTIVE: To identify novel genetic associations with white matter hyperintensities (WMH). METHODS: We performed a genome-wide association meta-analysis of WMH volumes in 11,226 individuals, including 8,429 population-based individuals from UK Biobank and 2,797 stroke patients. Replication of novel loci was performed in an independent dataset of 1,202 individuals. In all studies, WMH were quantified using validated automated or semi-automated methods. Imputation was to either the Haplotype Reference Consortium or 1,000 Genomes Phase 3 panels. RESULTS: We identified a locus at genome-wide significance in an intron of PLEKHG1 (rs275350, β [SE] = 0.071 [0.013]; p = 1.6 × 10-8), a Rho guanine nucleotide exchange factor that is involved in reorientation of cells in the vascular endothelium. This association was validated in an independent sample (overall p value, 2.4 × 10-9). The same single nucleotide polymorphism was associated with all ischemic stroke (odds ratio [OR] [95% confidence interval (CI)] 1.07 [1.03-1.12], p = 0.00051), most strongly with the small vessel subtype (OR [95% CI] 1.09 [1.00-1.19], p = 0.044). Previous associations at 17q25 and 2p16 reached genome-wide significance in this analysis (rs3744020; β [SE] = 0.106 [0.016]; p = 1.2 × 10-11 and rs7596872; β [SE] = 0.143 [0.021]; p = 3.4 × 10-12). All identified associations with WMH to date explained 1.16% of the trait variance in UK Biobank, equivalent to 6.4% of the narrow-sense heritability. CONCLUSIONS: Genetic variation in PLEKHG1 is associated with WMH and ischemic stroke, most strongly with the small vessel subtype, suggesting it acts by promoting small vessel arteriopathy.This work was supported by a British Heart Foundation Programme Grant (RG/16/4/32218). Hugh Markus is supported by a National Institute for Health Research (NIHR) Senior Investigator award, and his work is supported by the Cambridge Universities NIHR Comprehensive Biomedical Research Centre. Loes Rutten-Jacobs was supported by a British Heart Foundation Immediate Research Fellowship (FS/15/61/31626). Natalia S. Rost is in part supported by NIH/NINDS R01NS086905 and R01NS082285. The MGH WMH study was supported by the National Institutes of Health (K23NS064052 - N.R.), American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N), and Deane Institute for Integrative Study of Atrial Fibrillation and Stroke. Robin Lemmens is a senior clinical investigator of FWO Flanders
Pathogenesis of Axonal Degeneration: Parallels Between Wallerian Degeneration and Vincristine Neuropathy
Joe Orton and Shakespeare: collage, class and queerness
This essay considers Joe Orton's relationship to Shakespeare through the library book covers that he redesigned with his partner Kenneth Halliwell and through his plays. It proposes that Orton and Halliwell's neglected Shakespeare dust jackets are as subversive as the better-known covers of the popular and middlebrow library books they reworked. Their collages ironise or queer Shakespeare's themes and contest critical authority. By focusing specifically on Arden editions, Orton and Halliwell resist the gentrification of Shakespeare engendered by elitist academic discourse and bourgeois spaces such as the public library and the theatre. The same irreverent attitude to Shakespeare is evident in Orton's plays. Although he admired, identified with and drew inspiration from his predecessor, Orton recycles Shakespeare's plots, lines and motifs to transform their class politics and to amplify their sexual dissidence. Overall, this essay contends that by reshaping Shakespeare from a working class, queer perspective Orton resists the Bard's growing function as an emblem of social distinction in mid-century Britain
Recommended from our members
Staging Beckett: constructing histories of performance
This multi-authored essay presents some selected initial findings from the AHRC Staging Beckett research project led by the universities of Reading and Chester with the Victoria and Albert Museum, London. For example, how did changes in economic and cultural climates, such as funding structures, impact on productions of Beckett's plays in the UK and Ireland from the 1950’s to the first decade of the twenty-first century? The essay raises historiographical questions raised by the attempts to map or construct performance histories of Beckett's theatre in the UK and Ireland
Towards sustainable tourism in the mediterranean? Policy and practice in Italy, Spain and Greece
Food crime, regulation and the biotech harvest
This article focuses on the trade and regulatory practices of transgenic or genetically modified (GM) food, or what Pringle (2003) refers to as the ‘biotech harvest’. It explores issues of eco-crime and raises questions for environmental and transnational justice when corporations and government are complicit in acts of economic exploitation and illegality