Validation of a Genome-Wide Polygenic Score for Obesity in South Asians

Obesity is a complex disorder, manifested by the interaction of inherited and environmental factors and modulated by a person’s lifestyle habits. India has witnessed more than two-fold increase in the number of overweight adults in the last 30 years. Polygenic risk score (PRS) quantitatively measures an individual’s risk for common diseases. PRS has been studied in obesity in Caucasian population and has not been validated in South Asian (SAS) population. In this study we validate the existing genome-wide PRS model of obesity with 2.1 million variants in SAS population. We analysed a total of 14,263 individuals from 3 different South Asian cohorts. We compare the risk score with the BMI categories (under-weight, normal weight, over-weight and obese) in all 3 cohorts. High BMI-PRS was associated with increased BMI in all the 3 cohorts. Top 10% high polygenic risk individuals constituted nearly twice the number of overweight and obese individuals as compared to normal BMI individuals in all the 3 cohorts. We conclude that high polygenic risk score is associated with high BMI in South Asians. Our study suggests that PRS score can perhaps be an early predictor of unhealthy weight gain in the South Asian population.