Clinical use of polygenic scores in type 2 diabetes: challenges and possibilities – published online 05/04/2025

Rashmi B. Prasad, Liisa Hakaste, Tiinamaija Tuomi

Once considered a ‘geneticist’s nightmare’, the genetic architecture of type 2 diabetes has been disentangled, with ~1200 variants identified that explain ~50% of its heritability, enabling construction of polygenic scores. In this issue, Prasad, Hakaste and Tuomi (https://doi.org/10.1007/s00125-025-06419-1) summarise current knowledge on type 2 diabetes-related polygenic scores (T2D-PGSs) in different ancestries and outline their possible clinical use. T2D-PGSs inform risk prediction and identification of individuals at high risk of comorbidities, and may provide predictive information for stratifying treatment response. The authors highlight, however, that a key challenge is the usability of T2D-PGSs across populations, as ancestry-specific genetic variation may impact the accuracy and applicability of these scores, hindering the integration of genetic data into current healthcare practices. In addition, knowledge gaps such as missing heritability and phenotypic heterogeneity challenge the clinical utility of PGSs. The authors conclude that, in the future, T2D-PGSs may be of most value in stratifying the severity of disease and treatment response, in addition to identification of the pathophysiological mechanisms involved. The figures from this review are available as a downloadable slideset.

All News