71 research outputs found

    The trans-ancestral genomic architecture of glycemic traits

    Get PDF
    Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

    Sounds like city

    No full text
    Anything in our world that moves vibrates air. If it moves in such a way that it oscillates at more than about 16 times a second this movement is heard as sound. The world, then, is full of sounds. (Schafer, 1969: 5) Auditory space has no favoured focus. It’s a sphere without fixed boundaries, space made by the thing itself, not space containing the thing. It is not pictorial space, boxed-in, but dynamic, always in flux, creating its own dimensions moment by moment. (Carpenter, 1973: 35) HOW DO we describe city spaces? There has been, in recent years,a prolixity of differing views on the treatment of this question inwhich two opposing general tendencies stand out: the reductionist and the phenomenological positions. Reductionist theorists argue that a city is no more than a lattice of physical enclosures, apertures, planes, inter-sections bound together by the regulatory force of the Cartesian grid. A phenomenological approach, on the other hand, can provide a theory of wider scope; it can include in the description of a city’s attributes the corpo-real, the sensual and psychological aspects of subjective experience, as well as the broader cultural characteristics of the different communities and subcultures which contribute to the diversity of city spaces. From this point of view, the reductionist position appears locked within its own rigidity, creating ossified spaces by relying on the method of deductive analysis, rather than on direct sensory experience. Non-reductive theories (of which there are many different kinds) align themselves with the notion that a city is not just the sum total of buildings and streets; indeed, it is not generated by the neat ontological division of container and contained: metaphorical space can supervene upon the physical divisions of the urban metropolis. The phenomenological view adopts a body-centred paradigm in which there is no clear dichotomy between the experiencing subject and th
    • …
    corecore