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- Evangelou, Evangelos, et al.
(författare)
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A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:12, s. 2130-2136
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
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| 2. |
- Ioannidis, Konstantinos, 1976-
(författare)
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Designing the Edge : An Inquiry into the Psychospatial Nature of Meaning in the Architecture of the Urban Waterfront
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The initial goal of this effort is to develop a discussion on urban design process and thinking that acknowledges the needs of places with meaning in the design of the urban waterfront. The thesis addresses the fact that the problematic of the coastal formulation is intricate, comprising not only aspects related to the spatial organization and design of its domain but also shared properties originated by the presence and movement of the perceiving subject in the area. In this framework, the research attempts to provide an understanding of the main relationships that the subject cultivates inside the coastal space and to offer a broader spatial reading of its narrative function. On the hypothesis that this function is susceptible of interpretation, the thesis develops an interest in examining the effects of the psychospatial nature of meaning on the design and experience of the urban edge, for to interpret a narrative spatial construct is to specify its meaning. To explore the issue of waterfront places that speak of the subject, the research conceives the coastal space as a field of mediated parameters that pertain to three crucial operational premises: the symbolic function of the urban space near the water, the meaning behind the coastal form, and the engagement of the perceiving subject in the conscious or reflexive appropriation of the waterfront setting. These premises, traced as psychophysiological spaces, determine the intermediary, the integrative, and the expressive discourses for the development of places with meaning near the water. Through them, the thesis attempts a reading of the coastal domain based upon the material interpretation of the meanings and messages associated with the immediate experience of the onset of water‐born notions, concepts, and images. Writing about the dialectics between the psychospatial inquiry and the spatial experience of the edge, this thesis suggests that, contrary to the established preconception, the psychology of human‐edge relations submits the perceiving subject to the conception of the coastal form and shape.
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