Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Voyage(s) to Sarajevo: Jean-Luc Godard and the Image of War

This essay discusses Jean-Luc Godard’s artistic response to the Bosnian War (1992-95), and its representations in the Western mass media. For Godard, the reluctance of Europe’s advanced liberal democracies to intervene meaningfully in Bosnia – their insistence that 'humanitarianism' rather than protective intervention was the order of the day – was tantamount to supporting Serbian fascism, and – a fortiori – regressing to a policy of appeasement reminiscent of the days of the Munich Agreement. Although Godard's stance set him against some of his former compatriots on the left, speculating on his ideological motivations is beside the point. Rather, it is is in his filmmaking, in his vision of cinema, and how it relates to other histories of the image, that Godard’s sensibility can be most keenly felt and understood. As the essay points out, even his recent contribution to Jean-Michel Frodon's compilation film, Bridges of Sarajevo/Les ponts de Sarajevo (2014, 114 mn.), persists in posing questions about how the past continues to shape the present, and how Sarajevo and its contemporary history still delineates the identity of Europe. 

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.

Sound Art and Spatial Practices: Situating Sound Installation Art Since 1958

This dissertation examines the emergence and development of sound installation art, an under-recognized tradition that has developed between music, architecture, and media art practices since the late 1950s. Unlike many musical works, which are concerned with organizing sounds in time, sound installations organize sounds in space; they thus necessitate new theoretical and analytical models that take into consideration the spatial situated-ness of sound. Existing discourses on “spatial sound” privilege technical descriptions of sound localization. By contrast, this dissertation examines the ways in which concepts of space are socially, culturally, and politically construed, and how spatially-organized sound works reflect and resist these different constructions. Using an interdisciplinary methodology of critical spatial analysis and critical studies in music, this dissertation explores such topics as: conceptions of acoustic space in postwar Western art music, architecture, and media theory; the development of sound installation art in relation to philosophies of everyday life and social space; the historical links between musical performance, conceptual art, and sound sculpture; the body as a site for sound installations; and sonicspatial strategies that confront politics of race and gender. Through these different investigations, this dissertation proposes an “ontopological” model for considering sound: a critical model of analysis and reception that privileges an understanding of sound in relation to ontologies of space and place.