title: A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population.
abstract: BACKGROUND
  Uric acid (UA) is a complex phenotype influenced by both genetic and environmental factors as well as their interactions. Current genome-wide association studies (GWASs) have identified a variety of genetic determinants of UA in Europeans; however, such studies in Asians, especially in Chinese populations remain limited.
  
  
  METHODS
  A two-stage GWAS was performed to identify single nucleotide polymorphisms (SNPs) that were associated with serum uric acid (UA) in a Chinese population of 12,281 participants (GWAS discovery stage included 1452 participants from the Dongfeng-Tongji cohort (DFTJ-cohort) and 1999 participants from the Fangchenggang Area Male Health and Examination Survey (FAMHES). The validation stage included another independent 8830 individuals from the DFTJ-cohort). Affymetrix Genome-Wide Human SNP Array 6.0 chips and Illumina Omni-Express platform were used for genotyping for DFTJ-cohort and FAMHES, respectively. Gene-environment interactions on serum UA levels were further explored in 10,282 participants from the DFTJ-cohort.
  
  
  RESULTS
  Briefly, we identified two previously reported UA loci of SLC2A9 (rs11722228, combined P = 8.98 × 10-31) and ABCG2 (rs2231142, combined P = 3.34 × 10-42). The two independent SNPs rs11722228 and rs2231142 explained 1.03% and 1.09% of the total variation of UA levels, respectively. Heterogeneity was observed across different populations. More importantly, both independent SNPs rs11722228 and rs2231142 were nominally significantly interacted with gender on serum UA levels (P for interaction = 4.0 × 10-2 and 2.0 × 10-2, respectively). The minor allele (T) for rs11722228 in SLC2A9 has greater influence in elevating serum UA levels in females compared to males and the minor allele (T) of rs2231142 in ABCG2 had stronger effects on serum UA levels in males than that in females.
  
  
  CONCLUSIONS
  Two genetic loci (SLC2A9 and ABCG2) were confirmed to be associated with serum UA concentration. These findings strongly support the evidence that SLC2A9 and ABCG2 function in UA metabolism across human populations. Furthermore, we observed these associations are modified by gender.
authors: Binyao
authors: B
authors: Yang
authors: Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei, China. zengnanmo@hotmail.com.
authors: Zengnan
authors: Z
authors: Mo
authors: Chen
authors: C
authors: Wu
authors: Handong
authors: H
authors: Yang
authors: Xiaobo
authors: X
authors: Yang
authors: Yunfeng
authors: Y
authors: He
authors: Lixuan
authors: L
authors: Gui
authors: Li
authors: L
authors: Zhou
authors: Huan
authors: H
authors: Guo
authors: Xiaomin
authors: X
authors: Zhang
authors: Jing
authors: J
authors: Yuan
authors: Xiayun
authors: X
authors: Dai
authors: Jun
authors: J
authors: Li
authors: Gaokun
authors: G
authors: Qiu
authors: Suli
authors: S
authors: Huang
authors: Qifei
authors: Q
authors: Deng
authors: Yingying
authors: Y
authors: Feng
authors: Lei
authors: L
authors: Guan
authors: Die
authors: D
authors: Hu
authors: Xiao
authors: X
authors: Zhang
authors: Tian
authors: T
authors: Wang
authors: Jiang
authors: J
authors: Zhu
authors: Xinwen
authors: X
authors: Min
authors: Mingjian
authors: M
authors: Lang
authors: Dongfeng
authors: D
authors: Li
authors: Frank B
authors: FB
authors: Hu
authors: Dongxin
authors: D
authors: Lin
authors: Tangchun
authors: T
authors: Wu
authors: Meian
authors: M
authors: He
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D002681:China; D005006:Ethnicity / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D015203:Reproducibility of Results; D012907:Smoking / Q000235:genetics; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D051246:Glucose Transport Proteins, Facilitative; D009363:Neoplasm Proteins; C411811:SLC2A9 protein, human; D014527:Uric Acid