The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao tong University (SJTU) School of Medicine, Shanghai, China.
Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clin Endocrinol (Oxf). 2018 Dec;89(6):840-848. doi: 10.1111/cen.13847. Epub 2018 Oct 1.
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.
Dense mapping studies based on GWAS.
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.
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.
After the first replication stage, four SNPs from three regions with P < 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 = 7.55 × 10 , OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 (P = 5.59 × 10 , 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.
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.
我们旨在研究从欧洲人群中发现的 6 个 GD 易感基因座，进一步估计这些基因座在我们 GD 患者分层中的遗传异质性。
基于 GWAS 的密集图谱研究。
GWAS 阶段共有 1536 名 GD 患者和 1516 名对照，两个复制阶段分别有 1994 名 GD 患者和 2085 名对照，5033 名 GD 患者和 5389 名对照。
基于我们之前的 GWAS 数据，通过 TagSNP 分析和逻辑回归分析，独立鉴定每个区域中与 GD 相关的 SNP。在 1994 名 GD 患者和 2085 名对照中研究这些 SNP 的相关性，然后在包括 5033 名 GD 患者和 5389 名对照的第二个队列中进一步对显著相关的 SNP（P<0.05）进行基因分型。
经过第一阶段的复制，三个区域中 P<0.05 的四个 SNP 被进一步选择，并在另一个独立队列中进行基因分型。在联合中国队列中，两个与 GD 相关的 SNP 得到了证实：11q21 上的 rs12575636（P=7.55×10，OR=1.27）和 2p25.1 上的 rs1881145 在 TRIB2 中（P=5.59×10，OR=1.14）。进一步的研究表明，这些 SNP 在 GD 亚组之间没有显著差异。然而，eQTL 数据显示，SESN3 可能是 11q21 区域 GD 的一个潜在易感基因。
在从欧洲人群中发现的 6 个 GD 易感基因座中，有两个风险基因座在一个大型汉族人群中得到了证实。不同种族之间的 GD 遗传易感性存在差异。SESN3 可能是 11q21 区域 GD 的一个潜在易感基因。
