12 research outputs found

    A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

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    dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

    Historic landscape character and sense of place

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    This is an Author's Accepted Manuscript of an article published in Landscape Research, 2013, Vol. 38, Issue 2 pp.179-202, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/01426397.2012.672642.Most studies of landscape character within archaeology and historical geography have focused on morphological features such as whether settlement patterns were nucleated or dispersed, but this paper discusses how adding depth to this, for example by studying place-names, vernacular architecture, and the territorial structures within which a landscape was managed in the past, gives us a far greater understanding of its texture and meaning to local communities. In two case-studies in southern Essex, for example, it is shown how the connections that once existed between inland and coastal communities can be used today to promote public access to the countryside. A further case study, in southwest England, shows how field-/place-names and vernacular architecture also make an important contribution to our appreciation of the time depth and complexity of landscape character.Arts and Humanities Research Council (AHRC)Southend-on-Sea Borough Counci
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