A dense mapping study of six European AITD susceptibility regions in a large Chinese Han Cohort of Graves' disease
A dense mapping study of six European AITD susceptibility regions in a large Chinese Han Cohort of Graves' disease
复制标题
对中国汉族格雷夫斯病大型人群中六个欧洲 AITD 易感区的密集绘图研究
DOI：
10.1111/cen.13847
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发表时间：
2018-12-01
影响因子：
3.2
通讯作者：
Song, Huai-Dong
中科院分区：
文献类型：
--
作者：
Liu, Wei;Zhang, Qian-Yue;Song, Huai-Dong
目的研究中国汉族人群中6个欧洲人群GD易感基因座的分布情况，并进一步分析其在中国GD患者分层中的遗传异质性。设计基于GWAS的密集映射研究。在GWAS阶段，总共有1536名GD患者和1516名对照，在两个重复阶段，总共有1994名GD患者和2085名对照，以及5033名GD患者和5389名对照。基于我们先前的GWAS数据，通过TagSNP分析和Logistic回归分析确定每个区域中独立的GD相关SNP。在1994例GD患者和2085例对照组中研究这些SNP的关联性，然后在第二队列包括5033例GD患者和5389例对照组中进一步对显著关联的SNP进行基因分型（P < 0.05）。结果在第一个重复阶段后，从三个区域中选择P-first < 0.05的4个SNP，并在另一个独立队列中进行基因分型。两个SNP与GD的相关性在合并的中国队列中得到证实：11 q21的rs 12575636（P-合并= 7.55 x 10（-11），OR = 1.27）和TRIB 2 2p25.1的rs 1881145（P-合并= 5.59 x 10（-8），OR = 1.14）。进一步的研究显示GD亚群之间的这些SNP无显著差异。eQTL分析结果表明，SESN 3可能是11 q21区域GD的一个潜在易感基因。结论在欧洲人群中发现的6个GD易感基因座中，有2个在中国汉族人群中发现。GD的遗传易感性在不同种族群体中存在差异。SESN 3是位于11 q21的GD的潜在易感基因。
Objective We aimed to investigate the six susceptibility loci of GD identified from European population in Chinese Han population and further to estimate the genetic heterogeneity of them in stratification of our GD patients. Design Dense mapping studies based on GWAS. Patients A total of 1536 GD patients and 1516 controls in GWAS stage and 1994 GD patients and 2085 controls and 5033 GD patients and 5389 controls in two replication stages. Measurements Based on our previous GWAS data, independently GD-associated SNPs in each region were identified by TagSNP analysis and logistic regression analysis. The association of these SNPs was investigated in 1994 GD patients and 2085 controls, and then, the significantly associated SNPs (P < 0.05) were further genotyped in a second cohort including 5033 GD patients and 5389 controls. Results After the first replication stage, four SNPs from three regions with P-first < 0.05 were further selected and genotyped in another independent cohort. The association of two SNPs with GD was confirmed in combined Chinese cohorts: rs12575636 at 11q21 (P-combined = 7.55 x 10(-11), OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 (P-combined = 5.59 x 10(-8), OR = 1.14). Further study disclosed no significant difference for these SNPs between GD subsets. However, eQTL data revealed that SESN3 could be a potential susceptibility gene of GD in 11q21 region. Conclusions Out of the six susceptibility loci of GD identified from European population, two risk loci were confirmed in a large Chinese Han population. There is variability in GD genetic susceptibility in different ethnic groups. SESN3 is a potential susceptible gene of GD in 11q21.