初步的全基因组关联研究鉴定了中国人群中与甲状腺相关激素相关的新易感基因。
Preliminary study of genome-wide association identified novel susceptibility genes for thyroid-related hormones in Chinese population.
机构信息
Hainan Affiliated Hospital of Hainan Medical University, #19, Xiuhua Road, Xiuying District, Haikou, 570311, Hainan, People's Republic of China.
Xincun Central Health Center, Lingshui Li Autonomous County, Lingshui, 572426, Hainan, People's Republic of China.
出版信息
Genes Genomics. 2022 Aug;44(8):1031-1038. doi: 10.1007/s13258-021-01165-1. Epub 2021 Sep 17.
BACKGROUND
Thyroid hormones are critical regulators of metabolism, development and growth in mammals. However, the genetic association of thyroid-related hormones in the Chinese Han population is not fully understood.
OBJECTIVE
We aimed to identify the genetic loci associated with circulating thyroid-related hormones concentrations in the healthy Chinese Han population.
METHODS
Genotyping was performed in 124 individuals using Applied Biosystems™ Axiom™ PMDA, and 796,288 single nucleotide polymorphisms (SNPs) were available for the GWAS analysis. For replication, eleven SNPs were selected as candidate loci for genotyping by Agena MassARRAY platform in additional samples (313 subjects). The values of p < 5 × 10 suggest a suggestively significant genome-wide association with circulating thyroid-related hormones concentrations.
RESULTS
We identified that rs11178277 (PTPRB, p = 4.88 × 10) and rs7320337 (LMO7DN-KCTD12, p = 1.22 × 10) were associated with serum FT3 level. Three SNPs (rs4850041 in LOC105373394-LINC01249: p = 3.55 × 10, rs6867291 in LINC02208: p = 2.40 × 10 and rs79508321 in WWOX: p = 3.35 × 10) were related to circulating T3 level. Rs12474167 (LOC105373394-LINC01249, p = 1.65 × 10) and rs1864553 (IWS1, p = 2.00 × 10) were associated with circulating T4 concentration. The association with TGA concentration was for rs17163542 in DISP1 (p = 3.46 × 10) and rs12601151 in NOG-C17orf67 (p = 2.72 × 10). Two genome-level significant SNPs (rs2114707 in LINC01314, p = 1.69 × 10 and rs12601151, p = 1.41 × 10) associated with serum TMA concentration were identified. Moreover, rs6083269 (CST1-CST2, p = 3.36 × 10) was a significant locus for circulating TSH level. In replication, rs12601151 in NOG-C17orf67 was still associated with serum TGA level (p = 0.012).
CONCLUSIONS
The GWAS reported 11 new suggestively significant loci associated with circulating thyroid-related hormones levels among the Chinese Han population. These findings represented suggestively biological candidates for circulating thyroid-related hormones levels and provided new insights into the mechanisms of regulating serum TGA concentration.
背景
甲状腺激素是哺乳动物代谢、发育和生长的关键调节剂。然而，在中国汉族人群中，与甲状腺相关激素相关的遗传关联尚未完全了解。
目的
我们旨在确定与健康中国汉族人群循环甲状腺相关激素浓度相关的遗传位点。
方法
使用 Applied Biosystems™ Axiom™ PMDA 在 124 个人中进行基因分型，并且 GWAS 分析中可利用 796,288 个单核苷酸多态性 (SNP)。为了复制，选择 11 个 SNP 作为候选基因座，通过 Agena MassARRAY 平台在另外的样本 (313 例) 中进行基因分型。p 值<5×10-5 提示与循环甲状腺相关激素浓度有显著的全基因组关联。
结果
我们发现 rs11178277 (PTPRB，p=4.88×10) 和 rs7320337 (LMO7DN-KCTD12，p=1.22×10) 与血清 FT3 水平有关。三个 SNP(rs4850041 在 LOC105373394-LINC01249：p=3.55×10，rs6867291 在 LINC02208：p=2.40×10 和 rs79508321 在 WWOX：p=3.35×10) 与循环 T3 水平有关。rs12474167 (LOC105373394-LINC01249，p=1.65×10) 和 rs1864553 (IWS1，p=2.00×10) 与循环 T4 浓度有关。rs17163542 在 DISP1(p=3.46×10) 和 rs12601151 在 NOG-C17orf67(p=2.72×10) 与 TGA 浓度有关。两个全基因组显著 SNP(rs2114707 在 LINC01314，p=1.69×10 和 rs12601151，p=1.41×10) 与血清 TMA 浓度有关。此外，rs6083269 (CST1-CST2，p=3.36×10) 是循环 TSH 水平的显著位点。在复制中，NOG-C17orf67 中的 rs12601151 仍与血清 TGA 水平有关(p=0.012)。
结论
GWAS 报告了 11 个新的与中国汉族人群循环甲状腺相关激素水平相关的提示性显著位点。这些发现代表了循环甲状腺相关激素水平的提示性生物学候选物，并为调节血清 TGA 浓度的机制提供了新的见解。
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