Replication of Gout/Urate Concentrations GWAS Susceptibility Loci Associated with Gout in a Han Chinese Population

Zhiqiang Li,Lin Han,Zhen Liu,Jie Lü ,Xinde Li,Ying Xin,Jianhua Chen,Leina Ma ,Xuefeng Wang,Xu Hou,Zhaotong Jia,Can Wang,Zhaowei Zhou,Jue Ji,Wei Ren,Yongyong Shi,Qing‐Sheng Mi ,Tian Liang ,Dajiang Lu,Keke Zhang,Xuan Yuan,Lingling Cui,Xiaoyu Cheng,Qing Yu,Changgui Li

doi:10.1038/s41598-017-04127-4

Abstract

Gout is a chronic disease resulting from elevated serum urate (SU). Previous genome-wide association studies (GWAS) have identified dozens of susceptibility loci for SU/gout, but few have been conducted for Chinese descent. Here, we try to extensively investigate whether these loci contribute to gout risk in Han Chinese. A total of 2255 variants in linkage disequilibrium (LD) with GWAS identified SU/gout associated variants were analyzed in a Han Chinese cohort of 1255 gout patients and 1848 controls. Cumulative genetic risk score analysis was performed to assess the cumulative effect of multiple “risk” variants on gout incidence. 23 variants (41%) of LD pruned variants set (n = 56) showed nominal association with gout in our sample (p < 0.05). Some of the previously reported gout associated loci (except ALDH16A1), including ABCG2, SLC2A9, GCKR, ALDH2 and CNIH2, were replicated. Cumulative genetic risk score analyses showed that the risk of gout increased for individuals with the growing number (≥8) of the risk alleles on gout associated loci. Most of the gout associated loci identified in previous GWAS were confirmed in an independent Chinese cohort, and the SU associated loci also confer susceptibility to gout. These findings provide important information of the genetic association of gout.

Highlights

Genetic studies for serum urate (SU)/gout have been conducted in Han Chinese[16,17,18,19]
11 of the significant variants were from the gout associated loci (GCKR, SLC2A9, ABCG2, CNIH2, MYL2-CUX2 (ALDH2) and BCAS3)
The CNIH2 and MYL2-CUX2 (ALDH2) loci are two novel gout loci identified in recent Japanese studies[14, 22]

Summary

Introduction

Genetic studies for SU/gout have been conducted in Han Chinese[16,17,18,19]. most of them examined only a small minority of loci. 11 of the significant variants were from the gout associated loci (GCKR, SLC2A9, ABCG2, CNIH2, MYL2-CUX2 (ALDH2) and BCAS3). We observed nominal associations at rs801733 (CNIH2, p = 0.026, OR = 0.428) and rs11066008 (MYL2-CUX2 (ALDH2), p = 2.94 × 10−3, OR = 0.666) (Table 1), which are in strong LD with the previously identified gout associated variants (rs4073582 and rs[671], r2 = 0.96 and 0.79, respectively), and the directions of effects for both variants were consistent with the previous reports[14, 22].

Results

Conclusion