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

About the Authors

The interdisciplinary nature of human-computer interaction (HCI) makes it possible to contribute towards an improved thinking in design and the process of information system designs. It is, however, a challenging aim, because the transformation of different gathered knowledge from HCI to information system designers is not easy, there being multiple design solutions available. In this paper a design space for designing an information system aimed at sustainability is introduced and discussed. The design space could be seen as part of a new design process, or correlating with an existing design setting and consisting of nine different components that are explored elaborately through a design space analysis. Differently selected dimensions of the proposed design space imitate knowledge from HCI and the result thus reflects a support for successfully transferring knowledge from HCI to the information system (IS) designers for improving a design process