Project background

The aim of TRANSLATE is to implement genetic information directly into patient care to improve diagnosis and treatment of non-autoimmune diabetes. This project is the first large-scale implementation of systematic genetic testing within a common, non-communicable, chronic disease in Denmark, and will spearhead efforts to advance personalized medicine in Denmark.

We will contribute to establishing technology, workflow, and evidence on how to implement and communicate actionable genetic information to clinicians and patients in a generalized format. These developments are pivotal for personalized medicine to reach broader clinical application.

Research background

Monogenic diabetes demonstrates the profound effect that correctly identifying the genetic architecture of a disease can have on clinical practice. In-house targeted sequencing data from 4500 diabetic patients and 6500 non-diabetic controls show that many rare variants are specific to the Danish population. Further analyses show that about 2% of unselected T2D patients and about 6% of GDM patients carry monogenic variants. Almost a third of these patients have functional variants in the GCK gene.

These patients have a life-long, mildly elevated blood glucose level that is resistant to treatment and does not lead to complications. These patients are essentially healthy and should not be treated, but lack of knowledge on the underlying genetic pathology inevitably leads to overtreatment, which is a burden on the patient and the healthcare sector.

Sequencing and the HNF1A gene

Another third of these patients have mutations in the HNF1A gene. These patients need treatment but can be better treated with sulphonylurea (SU), which is cost-effective and imposes fewer risks and burdens on the patient, but is increasingly rarely used due to the emergence of newer drugs. The described variants are person-specific and can only be identified by sequencing.

Unfortunately, sequencing is not offered to the general diabetes population so carriers of these rare variants will not be identified and the correct diagnosis and treatment will not be implemented in daily routine.

Purpose

The purpose of TRANSLATE is therefore to introduce cost-effective sequencing technology, which enables the use of WGS as a standard diagnostic method and it will capitalize on already generated Danish reference data on selected diabetes genes.

Sequencing also enables detection of variants in non-coding genetic regions and structural variants, which adds new dimensions to genetic regions by facilitating study of novel types of genetic regulation.

The sequencing data will be translated into genetic results with a clinical application, thereby help to mitigate the shortage and costs of personnel qualified to translate genetic information into clinically applicable information, and improve response times.

Vision

Our vision is that by the end of the study, we will have developed pipelines that obviate the need for us to manually handle genetic information in diabetes and subsequently other diseases.