We used a 3-stage approach to construct an obesity GRS from GWAS results. Our tests of this obesity GRS in the population-based ARIC cohort revealed it to be a highly statistically significant predictor of BMI measured at 4 time points across 10 years, of weight and waist-circumference, and of obesity. In terms of value added, the GRS improved prediction of BMI and obesity over and above demographic and geographic information, FTO and MC4R genotypes, and information about socioeconomic status. Thus, the GRS provides a measure of genetic predisposition to obesity that could inform etiological and treatment research. Finally, the GRS was associated with mortality risk. Interestingly, higher mortality risk for individuals with higher GRSs did not depend on their BMI.
