Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3
Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3
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DOI：
10.1038/ng.2367
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发表时间：
2012-09-01
期刊：
影响因子：
30.8
通讯作者：
Kung, Annie W. C.
中科院分区：
文献类型：
--
作者：
Cheung, Ching-Lung;Lau, Kam-Shing;Kung, Annie W. C.
甲状腺毒性周期性麻痹（TPP）是甲状腺毒症的一种可能危及生命的并发症。我们对123名中国南方TPP患者和1,170名健康对照者进行了全基因组关联研究（GWAS）和重复研究，并在染色体17q24.3上靠近KCNJ 2的位置确定了一个易感位点（rs312691：比值比（OR）= 3.3; P荟萃分析= 1.8 x 10（-14））。所有TPP受试者也患有Graves病，随后的TPP与Graves病的比较证实了17q24.3的关联是TPP特有的。rs312691基因型预测Graves病受试者TPP风险的曲线下面积（AUC）为0.73。表达数量性状基因座（eQTL）分析确定了可能影响KCNJ 2表达的rs312691（+/- 10 kb）侧翼区域的SNP（P = 0.0001）。我们的研究已经确定了与TPP相关的易感基因座，并提供了TPP的原因。
Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of thyrotoxicosis. We conducted a genome-wide association study (GWAS) and a replication study with a total of 123 southern Chinese with TPP (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (rs312691: odds ratio (OR) = 3.3; Pmeta-analysis = 1.8 x 10(-14)). All subjects with TPP also had Graves' disease, and subsequent TPP versus Graves' disease comparison confirmed that the association at 17q24.3 was specific to TPP. The area under the curve (AUC) of rs312691 genotype for risk prediction of TPP in subjects with Graves' disease was 0.73. Expression quantitative trait locus (eQTL) analysis identified SNPs in the region flanking rs312691 (+/- 10 kb) that could potentially affect KCNJ2 expression (P = 0.0001). Our study has identified a susceptibility locus associated with TPP and provides insight into the causes of TPP.