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A dense mapping study of six European AITD susceptibility regions in a large Chinese Han Cohort of Graves’ disease
Author(s) -
Liu Wei,
Zhang QianYue,
Yuan FeiFei,
Wang HaiNing,
Zhang LeLe,
Ma YuRu,
Ye XiaoPing,
Zhang ManMan,
Song ZhiYi,
Li ShengXian,
Du WenHua,
Liang Jun,
Zhang XiaoMei,
Gao GuanQi,
Zhao ShuangXia,
Chen Fengling,
Song HuaiDong
Publication year - 2018
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13847
Subject(s) - single nucleotide polymorphism , genome wide association study , cohort , population stratification , logistic regression , medicine , genetic association , population , genetics , oncology , genetic predisposition , expression quantitative trait loci , case control study , biology , genotype , disease , gene , environmental health
Summary 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 × 10 −11 , OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 ( P combined = 5.59 × 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 .