We tested differences between the predictiveness metrics for different risk scores by bootstrapping confidence intervals around the R2 and AUC metrics (comparing the difference in estimated metric values across 1,000 random samples drawn with replacement from the ARIC database 37) and by applying Pencina’s method 38 to test change in the IDI metric. Comparisons were as follows: Un-Weighted GRS vs. Weighted GRS; Weighted GRS vs. Simple Genetic Risk Assessment (the sum of risk alleles at the two best-replicated obesity loci, in the gene FTO and downstream of the gene MC4R, rs9939609 and rs12970134, respectively); Weighted GRS vs. Socioeconomic Index (Educational attainment measured in 5 categories: grade-school or less, some high school, high school graduate, vocational school, college, graduate/professional school, Supplementary Table 8).
