The trans-ancestral genomic architecture of glycemic traits

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

DESA1002 'Continuous City' Michael Buddee

I chose to design a Juvenile Detention Centre because in a city like Jerusalem that is so unstable and constantly filled with conflict a lot of this tension is bound to effect the youth. This may lead to uncharacteristically violent and anti-social behavior from the children. Therefore there needs to be a centre set up that can deal with these kids that have lost their way. This Juvenile Detention centre has been designed with a focus on rehabilitation rather than oppression and punishment. The centre has been designed to get de-railed youth back on track rather than continually punishing them, which can lead to them being embedded in a continuing cycle of criminal activity. The main goal of the centre is for the prisoners to leave the centre as mature young men who have the skills and capabilities necessary to contribute to the community. With large spaces and high light penetration the prison takes advantage of its hilltop position, opening its façade to an expansive view of Jerusalem allowing the prisoners to feel a degree of freedom whilst in confinement. This further emphasizes the philosophy of the centre focused on rehabilitation. Constructive activities are encouraged with plenty of space dedicated to productive outlets such as the wood workshop, rooftop garden, classrooms and gym area which is also on the rooftop. The façade works its way from closed confined spaces at one end to very open spaces at the other which is a metaphor for the inmates journey to once again be able to contribute to the community

Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P &lt; 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with &gt;50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background