Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.

Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index.

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.

A Multi-SNP Locus-Association Method Reveals a Substantial Fraction of the Missing Heritability.

There are many known examples of multiple semi-independent associations at individual loci; such associations might arise either because of true allelic heterogeneity or because of imperfect tagging of an unobserved causal variant. This phenomenon is of great importance in monogenic traits but has not yet been systematically investigated and quantified in complex-trait genome-wide association studies (GWASs). Here, we describe a multi-SNP association method that estimates the effect of loci harboring multiple association signals by using GWAS summary statistics. Applying the method to a large anthropometric GWAS meta-analysis (from the Genetic Investigation of Anthropometric Traits consortium study), we show that for height, body mass index (BMI), and waist-to-hip ratio (WHR), 3%, 2%, and 1%, respectively, of additional phenotypic variance can be explained on top of the previously reported 10% (height), 1.5% (BMI), and 1% (WHR). The method also permitted a substantial increase (by up to 50%) in the number of loci that replicate in a discovery-validation design. Specifically, we identified 74 loci at which the multi-SNP, a linear combination of SNPs, explains significantly more variance than does the best individual SNP. A detailed analysis of multi-SNPs shows that most of the additional variability explained is derived from SNPs that are not in linkage disequilibrium with the lead SNP, suggesting a major contribution of allelic heterogeneity to the missing heritability.

Excluding exceptions: Housing non-affordability and the oppression of environmental sustainability?

This paper explores the provision of homes for less wealthy households in rural England. By allowing 'exceptions' to UK planning law to provide low-income housing for local residents, the national government seeks to secure dwellings for the less wealthy and so sustain socially mixed rural villages. This paper explores how the production of homes through the exception policy is not conducive to the construction of many new houses. The particular emphasis in the paper is on how responsible agents are discouraged from being more active in erecting new village homes for low-income households. Empirically, the paper draws on documents, interviews and a social survey in the counties of Bedfordshire, Cambridgeshire and Norfolk to investigate the process of delivering rural exception homes. It is concluded that, despite Government assertions that a socially mixed countryside is desirable, the decision-making criteria that dominate the worldviews of agents in social housing provision work against this outcome. (c) 2005 Elsevier Ltd. All rights reserved.

Multiculturalismo, diversidade cultural e cotidiano escolar: uma análise da temática em filmes de escola

This work has as its theme the multiculturalism, cultural diversity and their reflections in school everyday, more specifically on the interactions between the various subjects and social groups that make up a school and the teacher as mediator of the relationship between these guys. The theme Multiculturalism refers in the first instance, to the theoretical movement beginning in the mid-20th century in the United States and that spreads in the Western world as a way of tackling the conflicts generated depending on the economic issues, policies, and, in particular, cultural-ethnic, in an attempt to combat discrimination and prejudice, given the difficulties of individuals and groups to welcome and socialize with the plurality and cultural differences (SILVA; BRANDIM, 2008).At the same time, multiculturalism refers to cultural studies, through the Centre for Contemporary cultural studies, founded by em1964 Hoggart, and connected to the English language Department of the University of Birmingham in England.In contemporary times, due to the phenomenon of globalization and public policy to challenge prejudice and discrimination the subjects and social groups, regardless of color, creed, ethnicity, sexual orientation and nationality, this theme has been recurring in order to recognize plural identities and ensure and directly affects the school as a place of cultural diversity and conflicts generated by the very diversity.The present work aims to analyze and understand how the issue of multiculturalism and cultural diversity in school films. Our study will be based theoretically in Cultural Studies authors and uses the qualitative approach, working with movie content analysis of school, seeking to seize on the same relations of coexistence, conflicts and the mediations of teachers

William Hogarth;

Appendix IV: The literary remains of "Ald Hoggart," the painter's uncle, p. 206-209.