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A genome wide association study of plasma uric acid levels in obese cases and never‐overweight controls
Author(s) -
Li WeiDong,
Jiao Hongxiao,
Wang Kai,
Zhang Clarence K.,
Glessner Joseph T.,
Grant Struan F.A.,
Zhao Hongyu,
Hakonarson Hakon,
Arlen Price R.
Publication year - 2013
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20303
Subject(s) - genome wide association study , uric acid , single nucleotide polymorphism , genetic association , quantitative trait locus , snp , biology , genetics , overweight , obesity , endocrinology , medicine , gene , genotype
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 .