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ImpactT2D: una estrategia genómica para implementar medicina de precisión en la diabetes tipo 2

Jorge Ferrer

Full genome sequences will become more widely available, but further study is needed to demonstrate their usefulness in common diseases such as type 2 diabetes (T2D). T2D affects ~14% of the Spanish adult population, and is one of the leading causes of mortality and healthcare spending. It is extremely heterogeneous but lacks markers to guide personalized therapeutic decisions. Polygenic risk scores (PRS) have the potential to discriminate different risk mechanisms for T2D. On the other hand, a small set of patients harbors coding mutations capable of guiding clinical decisions. The DecodeDiabetes study has identified non-coding mutations shared by patients with monogenic diabetes and T2D. ImpactT2D will deploy a strategy to demonstrate the clinical applicability of genomic information in T2D.

To this end:
1. Will generate complete genomes from a unique cohort of 1000 patients (cohort1). In Cohort 1, with a T2D subphenotype that maximizes genetic load, partitioned PRS and causal rare variants will be defined, and AI tools will be used to develop stratification models. 
2. It will generate a second validation cohort (cohort 2). Cohort 2, defined with broader phenotypic criteria, will be sequenced using panels. With it, he will validate stratification models, and study differences in pharmacological responses at the extremes of the polygenic spectrum. 
3. It will implement mechanisms to integrate it into the health system. 

ImpactT2D is aligned with precision medicine and genomics initiatives in T2D in Spanish and international health centers. It leverages a network of primary care, clinical investigators, clinical and genomics cohorts directly relevant to the project, as well as multidisciplinary expertise in AI, clinical trials, genomics, and genetics. The strategy aims to provide transformative findings for precision medicine in T2D.