A genome-wide association study of serum uric acid in African Americans

African American (AA) participants (n = 1,017) from the Howard University Family Study were included in this study. Genotyping was performed using the Affymetrix？ Genome-wide Human SNP Array 6.0. Imputation was performed using MACH and the HapMap reference panels for CEU and YRI. A total of 2,400,542 single nucleotide polymorphisms (SNPs) were assessed for association with serum uric acid under the additive genetic model with adjustment for age, sex, BMI, glomerular filtration rate, HTN, T2D, and the top two principal components identified in the assessment of admixture and population stratification.Four variants in the gene SLC2A9 achieved genome-wide significance for association with SUAL (p-values ranging from 8.88 × 10-9 to 1.38 × 10-9). Fine-mapping of the SLC2A9 signals identified a 263 kb interval of linkage disequilibrium in the HapMap CEU sample. This interval was reduced to 37 kb in our AA and the HapMap YRI samples.The most strongly associated locus for SUAL in EA populations was also the most strongly associated locus in this AA sample. This finding provides evidence for the role of SLC2A9 in uric acid metabolism across human populations. Additionally, our findings demonstrate the utility of following-up EA populations GWAS signals in African-ancestry populations with weaker linkage disequilibrium.In humans, uric acid is the primary byproduct of purine metabolism and has long been associated with the development of gouty arthritis [1,2]. Since the late 1800 s, it has been postulated that hyperuricemia plays a role in gout, kidney dysfunction, and vascular tone [3]. Over the past several decades, evidence linking uric acid to body mass index (BMI), insulin resistance, the metabolic syndrome, [4,5], dietary intake of food substances high in purine [1], dietary fructose intake [2,6,7], renal disease and hypertension [8-12] has been expanding.Clustering of uric acid, gout, renal disease, and hypertension has been known to have familial links since the late 1