Genome-wide association study identifies a novel susceptibility gene for serum TSH levels in Chinese populations
Genome-wide association study identifies a novel susceptibility gene for serum TSH levels in Chinese populations
复制标题
全基因组关联研究确定了中国人群血清 TSH 水平的新易感基因
DOI：
10.1093/hmg/ddu250
复制
发表时间：
2014-10-15
影响因子：
3.5
通讯作者：
Song, Huai-Dong
中科院分区：
文献类型：
--
作者：
Zhan, Ming;Chen, Gang;Song, Huai-Dong
促甲状腺激素(TSH)是甲状腺功能的敏感指标。高TSH水平和低TSH水平分别反映了甲状腺功能减退和甲状腺功能亢进。即使在正常范围内，TSH水平的微小差异(约0.5-1.0mU/i)也与血压、BMI、血脂异常、房颤和动脉粥样硬化的风险显著相关。TSH水平的大部分变化被认为是受遗传影响的。我们对1346名中国汉族个体进行了TSH水平的全基因组关联研究。在复制研究中，我们在一个独立的孤立的中国SHE队列(n=3235)中，对四个具有最高关联信号的候选SNPs进行了基因分型。我们在XKR4的8q12.1处发现了一个新的血清TSH易感基因座(rs2622590，P组合=2.21×10(-10))，并确认了先前报道的两个TSH易感基因座，分别位于FOXE1的9q22.33和CAPZB的1p36.13附近。Rs2622590_T等位基因和rs925489_C等位基因与低促甲状腺激素水平相关(rs2622590_T和925489_C分别为OR=1.41，P=0.014和OR=1.61，P=0.030)。在PTC组织中，rs2622590和rs925489基因分型分别与FOXE1和XKR4的表达水平相关(P=2.41×10~(-4)和P=0.02)。我们的发现表明，XKR4和FOXE1附近的SNP参与了TSH水平的调节。
Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function. High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively. Even within the normal range, small differences in TSH levels, on the order of 0.5-1.0 mU/I, are associated with significant differences in blood pressure, BMI, dyslipidemia, risk of atrial fibrillation and atherosclerosis. Most of the variance in TSH levels is thought to be genetically influenced. We conducted a genome-wide association study of TSH levels in 1346 Chinese Han individuals. In the replication study, we genotyped four candidate SNPs with the top association signals in an independent isolated Chinese She cohort (n = 3235). We identified a novel serum TSH susceptibility locus within XKR4at 8q12.1 (rs2622590, P-combined = 2.21 x 10(-10)), and we confirmed two previously reported TSH susceptibility loci near FOXE1 at 9q22.33 and near CAPZB at 1p36.13, respectively. The rs2622590_T allele at XKR4 and the rs925489_C allele near FOXE1 were correlated with low TSH levels and were found to be nominally associated to patients with papillary thyroid carcinoma (PTC) (OR = 1.41, P = 0.014 for rs2622590_T, and OR = 1.61, P = 0.030 for rs925489_C). The rs2622590 and rs925489 genotypes were also correlated with the expression levels of FOXE1 and XKR4, respectively, in PTC tissues (P = 2.41 x 10(-4) and P = 0.02). Our findings suggest that the SNPs in XKR4 and near FOXE1 are involved in the regulation of TSH levels.