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.

Finding revelation in anthropology: Alexander Winchell, William Robertson Smith and the heretical imperative

Anthropological inquiry has often been considered an agent of intellectual secularization. Not least is this so in the sphere of religion, where anthropological accounts have often been taken to represent the triumph of naturalism. This metanarrative however fails to recognise that naturalistic explanations could sometimes be espoused for religious purposes and in defence of confessional creeds. This essay examines two late nineteenth-century figures – Alexander Winchell in the United States, and William Robertson Smith in Britain – who found in anthropological analysis resources to bolster rather than undermine faith. In both cases these individuals found themselves on the receiving end of ecclesiastical censure and were dismissed from their positions at church-governed institutions. But their motivation was to vindicate divine revelation, in Winchell’s case from the physical anthropology of human origins and in Smith’s from the cultural anthropology of Semitic ritual.

Law's Ethical, Global and Theoretical Contexts: Essays in Honour of William Twining

Law's Ethical, Global and Theoretical Contexts examines William Twining's principal contributions to law and jurisprudence in the context of three issues which will receive significant scholarly attention over the coming decades. Part I explores human rights, including torture, the role of evidence in human rights cases, the emerging discourse on 'traditional values', the relevance of 'Southern voices' to human rights debates, and the relationship between human rights and peace agreements. Part II assesses the impact of globalization through the lenses of sociology and comparative constitutionalism, and features an analysis of the development of pluralistic ideas of law in the context of privatization. Finally, Part III addresses issues of legal theory, including whether global legal pluralism needs a concept of law, the importance of context in legal interpretation, the effect of increasing digitalization on legal theory, and the utility of feminist and postmodern approaches to globalization and legal theory.

Facilitating a culture of responsible and effective sharing of cancer genome data

Rapid and affordable tumor molecular profiling has led to an explosion of clinical and genomic data poised to enhance the diagnosis, prognostication and treatment of cancer. A critical point has now been reached at which the analysis and storage of annotated clinical and genomic information in unconnected silos will stall the advancement of precision cancer care. Information systems must be harmonized to overcome the multiple technical and logistical barriers to data sharing. Against this backdrop, the Global Alliance for Genomic Health (GA4GH) was established in 2013 to create a common framework that enables responsible, voluntary and secure sharing of clinical and genomic data. This Perspective from the GA4GH Clinical Working Group Cancer Task Team highlights the data-aggregation challenges faced by the field, suggests potential collaborative solutions and describes how GA4GH can catalyze a harmonized data-sharing culture.