Background: Cardiovascular disease, diabetes, and kidney disease are among the leading causes of death and disability worldwide. However, knowledge of genetic determinants of those diseases in African Americans remains limited. Results: In our study, associations between 4956 GWAS catalog reported SNPs and 67 traits were examined among 7726 African Americans from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which is focused on identifying factors that increase stroke risk. The prevalent and incident phenotypes studied included inflammation, kidney traits, cardiovascular traits and cognition. Our results validated 29 known associations, of which eight associations were reported for the first time in African Americans. Conclusion: Our cross-racial validation of GWAS findings provide additional evidence for the important roles of these loci in the disease process and may help identify genes especially important for future functional validation.