Development of a genetic risk score for type 1 diabetes

The causes of type 1 diabetes (T1D) are complex and not fully understood. What is known is that there is a genetic component to developing T1D – but who is at greater risk?

JDRF Canada is pleased to announce a new JDRF grant to support Dr. Despoina Manousaki, pediatric endocrinologist and genetic epidemiologist at Sainte-Justine Hospital in Montreal, that will allow her and her team to explore how the genome of an individual can predict the risk of developing type 1 diabetes (T1D). The more we can understand about the genetic predisposition of T1D, the more effectively we can screen for this risk and develop therapies to halt or delay the progression of the disease.

Dr. Manousaki, a former JDRF postdoctoral fellow, leads a research program focused on the genetics of complex disease in childhood.

How do genetic risk scores for type 1 diabetes work?

Existing genetic risk scores for T1D were largely developed using data from White European populations, which differ substantially from Canada’s diverse population. In her new JDRF-funded project, Dr. Manousaki will develop a trans-ancestral polygenic risk score for T1D, in simpler terms – looking at how different ancestral backgrounds and genetics influence the risk of developing T1D. These newly developed risk scores will be used in research and clinical practice to assess T1D in a more equitable manner. Since the existing polygenic risk scores perform poorly in diverse ancestral populations (as they were developed primarily in White European populations), there is a need to diversify these scores, particularly for T1D-related genes which are known to vary between people of different ancestral backgrounds.

Dr. Manousaki will use machine learning approaches that employ computers and algorithms to examine large European genetic datasets while incorporating genetic information from African, Indian, Latino, South-East Asian and Chinese ancestries. This will create more precise individual risk estimates of developing T1D, an important step for informing T1D screening in a diverse population. By having a better understanding of who might develop T1D, clinical teams can better select candidates across diverse Canadian populations for clinical monitoring as well as T1D prevention trials.

With the recent FDA approval of teplizumab (brand name Tzield), the first ever disease-modifying therapy that can delay the onset of T1D, research like that performed by Dr. Manousaki and her team will ensure that new T1D therapies are tested and applied appropriately in the diverse Canadian T1D community.

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