Genome-wide polygenic risk score for type 2 diabetes in Indian population

Area of Science:

• Genetics
• Public Health
• Personalized Medicine

Background:

• Genome-wide polygenic risk scores (PRS) are valuable for early identification of individuals at risk for lifestyle disorders like Type 2 Diabetes (T2D).
• Developing population-specific PRS is crucial for accurate risk prediction and targeted interventions.

Purpose of the Study:

• To develop and validate a polygenic risk score (PRS) for Type 2 Diabetes (T2D) specifically for the Indian population.
• To assess the PRS's efficacy in identifying individuals at risk for T2D within the Indian demographic.

Main Methods:

• Utilized imputed genotype data from UK Biobank for 959 T2D cases and 2,818 controls of Indian ancestry to develop the PRS.
• Employed summary statistics from the DIAMANTE consortium (South Asian data) to weight genetic variants and the LDpred2 algorithm to account for linkage disequilibrium.
• Validated the developed PRS on an independent Indian dataset (GenomegaDB) comprising 445 individuals.

Main Results:

• The PRS demonstrated significant association with T2D in the development cohort (AUC=0.7953, OR=2.9856), with the highest PRS quartile showing a 5.79-fold increased risk.
• The PRS also showed significant association in the independent Indian test dataset (AUC=0.7781, OR=1.6656).
• Higher PRS quartiles were sequentially associated with increased odds of developing T2D.

Conclusions:

• A framework for deriving Indian-specific PRS for T2D has been successfully established.
• The developed PRS shows potential as a prognostic metric for stratifying individuals based on T2D risk.
• The findings support the use of PRS for recommending personalized preventive strategies for Type 2 Diabetes in the Indian population.