12 research outputs found

    Lack of association between polymorphisms of the IL18R1 and IL18RAP genes and cardiovascular risk: the MORGAM Project

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    <p>Abstract</p> <p>Background</p> <p>Interleukin-18 is a pro-inflammatory cytokine suspected to be associated with atherosclerosis and its complications. We had previously shown that one single nucleotide polymorphism (SNP) of the <it>IL18 </it>gene was associated with cardiovascular disease (CVD) through an interaction with smoking. As a further step for elucidating the contribution of the IL-18 pathway to the etiology of CVD, we here investigated the association between the genetic variability of two IL-18 receptor genes, <it>IL18R1 </it>and <it>IL18RAP</it>, with the risk of developing CVD.</p> <p>Methods</p> <p>Eleven tagging SNPs, 5 in <it>IL18R1 </it>and 6 in <it>IL18RAP</it>, characterizing the haplotypic variability of the corresponding genes; were genotyped in 5 European prospective CVD cohorts including 1416 cases and 1772 non-cases, as part of the MORGAM project. Both single-locus and haplotypes analyses were carried out to investigate the association of these SNPs with CVD.</p> <p>Results</p> <p>We did not find any significant differences in allele, genotype and haplotype frequencies between cases and non-cases for either of the two genes. Moreover, the search for interactions between SNPs located in different genes, including 5 <it>IL18 </it>SNPs previously studied in the MORGAM project, and between SNPs and environmental factors remained unfruitful.</p> <p>Conclusion</p> <p>Our analysis suggests that the variability of <it>IL18R1 </it>and <it>IL18RAP </it>genes are unlikely to contribute to modulate the risk of CVD.</p

    The Roles of the Dystrophin-Associated Glycoprotein Complex at the Synapse

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    Dreaming fairness and re-imagining equality and diversity through participative aesthetic inquiry

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    © The Author(s) 2013. This article presents the findings of a participative action research project into how arts-based inquiry can revitalise equality and diversity organisational practices. We demonstrate that the arts-based methodologies introduced enabled participants to explore the meanings they brought to equality and diversity work, by creating a liminal space for learning. We illustrate our findings through an exploration of how participants engaged with the inquiry, the learning about equality and diversity that took place in the workshops and the challenges and opportunities of translating this into change practice in the workplace. The article’s originality lies in its analysis of poetic writings, dreams and visual artefacts created in the context of participative inquiry. Engaging with tacit knowledge extended understanding of the contribution that arts-based, aesthetic inquiry can bring to organisational practice, and more specifically towards restoring the transformative potential of organisational practices to promote equality and diversity

    Canonical correlation analysis for gene-based pleiotropy discovery.

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    Genome-wide association studies have identified a wealth of genetic variants involved in complex traits and multifactorial diseases. There is now considerable interest in testing variants for association with multiple phenotypes (pleiotropy) and for testing multiple variants for association with a single phenotype (gene-based association tests). Such approaches can increase statistical power by combining evidence for association over multiple phenotypes or genetic variants respectively. Canonical Correlation Analysis (CCA) measures the correlation between two sets of multidimensional variables, and thus offers the potential to combine these two approaches. To apply CCA, we must restrict the number of attributes relative to the number of samples. Hence we consider modules of genetic variation that can comprise a gene, a pathway or another biologically relevant grouping, and/or a set of phenotypes. In order to do this, we use an attribute selection strategy based on a binary genetic algorithm. Applied to a UK-based prospective cohort study of 4286 women (the British Women's Heart and Health Study), we find improved statistical power in the detection of previously reported genetic associations, and identify a number of novel pleiotropic associations between genetic variants and phenotypes. New discoveries include gene-based association of NSF with triglyceride levels and several genes (ACSM3, ERI2, IL18RAP, IL23RAP and NRG1) with left ventricular hypertrophy phenotypes. In multiple-phenotype analyses we find association of NRG1 with left ventricular hypertrophy phenotypes, fibrinogen and urea and pleiotropic relationships of F7 and F10 with Factor VII, Factor IX and cholesterol levels
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