3-stage approach is described in detail in the supplemental material. Analyses described in the supplemental material revealed that the 3-stage approach created GRSs that were at least as predictive of BMI and obesity as GRSs created with the top-hits and best-guess approaches. Further analyses to refine the 3-stage approach GRS yielded a final set of 32 SNPs (see supplemental material). We applied 2 weighting schemes to the 32 SNPs before summing them to create our obesity GRS: 1) equal weighting, under which the score was a simple count of BMI-increasing alleles; and 2) effect-size weighting, under which BMI-increasing alleles were weighted by the effect size reported for that locus in the GIANT Consortium 31 or DeCode 32 BMI GWAS. Effect-size weights were adjusted for LD between the SNP tested in the GWAS and the SNP genotyped in the ARIC sample. Each of the 32 SNPs in the GRS was missing for fewer than 1% of participants in any gender/ethnicity cell. GRSs were prorated by dividing the GRS by the number of SNPs contributing data and multiplying by 32. The SNPs included in the final obesity GRS, their BMI-increasing (“effect”) alleles, nearby genes, and weights are reported in Table 1.
