A genome wide association study of plasma uric acid levels in obese cases and never‐overweight controls

Objective To identify plasma uric acid‐related genes in extremely obese and normal weight individuals using genome‐wide association studies (GWASs). Design and Methods Using genotypes from a GWAS focusing on obesity and thinness, quantitative trait association analyses (PLINK) for plasma uric acid levels in 1,060 extremely obese individuals (BMI > 35 kg/m 2 ) and normal‐weight controls (BMI < 25kg/m 2 ) were performed. In 961 samples with uric acid data, 924 were females. Results Significant associations were found in SLC2A9 gene SNPs and plasma uric acid levels (rs6449213, P = 3.15 × 10 –12 ). DIP2C gene SNP rs877282 also reached genome‐wide significance ( P = 4.56 × 10 –8 ). Weaker associations ( P < 1× 10 –5 ) were found in F5 , PXDNL , FRAS1 , LCORL , and MICAL2 genes. Besides SLC2A9 , three previously identified uric acid‐related genes ABCG2 (rs2622605, P = 0.0026), SLC17A1 (rs3799344, P = 0.0017), and RREB1 (rs1615495, P = 0.00055) received marginal support in our study. Conclusions Two genes/chromosome regions reached genome‐wide association significance ( P < 1 × 10 –7 , 550K SNPs) in our GWAS: SLC2A9 , the chromosome 2 60.1 Mb region (rs6723995), and the DIP2C gene region. Five other genes ( F5 , PXDNL , FRAS1 , LCORL , and MICAL2 ) yielded P < 1 × 10 –5 . Four previous reported associations were replicated in our study, including SLC2A9 , ABCG2 , RREB , and SLC17A1 .