Genome-wide Polygenic Risk Score for Type 2 Diabetes in Indian Population

ABSTRACT Genome-wide polygenic risk scores (PRS) for lifestyle disorders, like Type 2 Diabetes (T2D), are useful in identifying at-risk individuals early on in life, and to guide them towards healthier lifestyles. The current study was aimed at developing PRS for the Indian population using imputed genotype data from UK Biobank and testing the developed PRS on data from GenomegaDB™ of Indians living in India. 984 T2D cases and 2,818 controls were selected from Indian participants of UK Biobank to develop the PRS. Summary statistics available for South Asians, from the DIAMANTE consortium, were used to weigh genetic variants. LDpred2 algorithm was used to adjust the effect of linkage disequilibrium among the variants. The association of PRS with T2D, tested with logistic regression, was found to be very significant (AUC = 0.75, OR = 3.06 [95%CI = 2.78 - 3.36]). When participants were divided into four PRS quartile groups, the odds of developing T2D increased sequentially with higher PRS groups. The highest PRS group (top 25%) showed 6.6 fold increased risk compared to the rest of the participants (75%). The derived PRS was found to be significantly associated with T2D in the test dataset of 446 Indians (AUC = 0.6, OR = 1.48 [95%CI = 1.21 - 1.8]). Our results indicate the importance of developing population-specific PRS for T2D to stratify the individuals, and to recommend personalized preventive measures.