Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Cockney, pseudo-slang et argot de série noire : San-Antonio et le moment Peter Cheyney du roman noir français

This article examines how in post-war France slang became a byword for the noir genre. It considers the mechanisms, models, networks and translators' practices which set the tone for the "Série Noire”, whose influence, both written and on the screen, had, within a decade, become, a "mythology" studied by Roland Barthes. It argues that this use of slang is redolent of the inauthenticity which characterises this stage in the reception of the Noir genre in France. It is certain that this artificial French slang is far from devoid of charm, or even mystery. But it tends to depreciate and deform the translated works and seems to be the hallmark of an era that might have defined and acclimatised Noir fiction in France, yet remains one which has not fully understood the gravity of its purpose. While such translations seem outdated nowadays (if not quite incomprehensible ), original works written at the time in French by writers inspired by the model of " pseudo- slang" and the fashionability of American popular culture have benefited from them. In this very inauthenticity, derivative novels have found a licence for invention and freedom, with authors such as Cocteau hailing it as a revival of the French written language. We see here how the adventures of Commissaire San Antonio, by Frédéric Dard constitute the best examples of this new creativity in French and draw upon a template set for the reception of American literature