Results should be considered in light of the following limitations: First, some ARIC participants were included in the samples of some of the GWAS used to construct the GRS. However, these ARIC participants represented a minority of the GWAS samples and results in the ARIC sample are similar to results from samples not included in any of the GWAS 29,30. Second, some risk loci identified by our 3-stage approach could only be genotyped in the ARIC sample using relatively weak proxies. Given the small improvement to predictiveness associated with each additional SNP included in the GRS, it is unlikely that this limitation influenced the substance of our results, but it is possible that our GRS is moderately more predictive than analyses in the ARIC cohort suggest. Third, our analyses were limited to African American and white Americans. The ARIC cohort does not contain Asian-descent or Hispanic individuals. It remains unclear whether the relatively greater similarity between these and European populations 50 would support the generalization of our GRS. However, GWAS of Asian and Hispanic samples 28,51 suggest that a European-descent
