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Preliminary study of genome-wide association identified novel susceptibility genes for thyroid-related hormones in Chinese population

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Abstract

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− 6 suggest a suggestively significant genome-wide association with circulating thyroid-related hormones concentrations.

Results

We identified that rs11178277 (PTPRB, p = 4.88 × 10− 07) and rs7320337 (LMO7DN-KCTD12, p = 1.22 × 10− 06) were associated with serum FT3 level. Three SNPs (rs4850041 in LOC105373394-LINC01249: p = 3.55 × 10− 06, rs6867291 in LINC02208: p = 2.40 × 10− 06 and rs79508321 in WWOX: p = 3.35 × 10− 06) were related to circulating T3 level. Rs12474167 (LOC105373394-LINC01249, p = 1.65 × 10− 06) and rs1864553 (IWS1, p = 2.00 × 10− 06) were associated with circulating T4 concentration. The association with TGA concentration was for rs17163542 in DISP1 (p = 3.46 × 10− 06) and rs12601151 in NOG-C17orf67 (p = 2.72 × 10− 07). Two genome-level significant SNPs (rs2114707 in LINC01314, p = 1.69 × 10− 06 and rs12601151, p = 1.41 × 10− 07) associated with serum TMA concentration were identified. Moreover, rs6083269 (CST1-CST2, p = 3.36 × 10− 06) 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.

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Funding

This study was funded by the Hainan Provincial Natural Science Foundation of China (819QN354), National Natural Science Foundation of China (No. 81660013 and No.81860015) and Key Research and Development Plan of Hainan Province (No. ZDYF2018116).

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Author notes

  1. Liang Huang and Fenghua Bai are co-first authors.

Authors and Affiliations

  1. Hainan Affiliated Hospital of Hainan Medical University, #19, Xiuhua Road, Xiuying District, Haikou, 570311, Hainan, People’s Republic of China

    Liang Huang, Fenghua Bai, Yutian Zhang, Xingwei Wei, Xiaoli Zhou, Mei Lin, Yufei Xie, Chanyi He, Qi Lin, Tian Xie & Yipeng Ding

  2. Xincun Central Health Center, Lingshui Li Autonomous County, Lingshui, 572426, Hainan, People’s Republic of China

    Liang Huang

  3. Science and Education Office, Hainan General Hospital, Haikou, 570311, Hainan, People’s Republic of China

    Fenghua Bai

  4. Department of General Practice, Hainan General Hospital, Haikou, 570311, Hainan, People’s Republic of China

    Yutian Zhang, Xingwei Wei, Xiaoli Zhou, Mei Lin, Yufei Xie, Chanyi He, Qi Lin & Yipeng Ding

  5. Xi’an 21st Century Biological Science and Technology Co., Ltd, Xi’an, 712000, Shaanxi, People’s Republic of China

    Shanshan Zhang & Tianbo Jin

  6. Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Haikou, 570311, Hainan, People’s Republic of China

    Tian Xie

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  1. Liang Huang
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Correspondence to Tian Xie or Yipeng Ding.

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Conflict of interest

Liang Huang, Fenghua Bai, Yutian Zhang, Shanshan Zhang, Tianbo Jin, Xingwei Wei, Xiaoli Zhou, Mei Lin, Yufei Xie, Chanyi He, Qi Lin, Tian Xie and Yipeng Ding declare that they have no conflict of interest.

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Supplementary Information

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13258_2021_1165_MOESM1_ESM.tif

Supplementary material 1 Regional plots of significant Loci associated with serum FT3 level.  Chromosomes are shown on the x-axis, and the − log10 p value on the y-axis. The color of each SNP spot, ranging from red to blue, reflects the degree of linkage disequilibrium (r2) with between other SNPs and top SNP (purple) (TIF 4657.8 kb)

13258_2021_1165_MOESM2_ESM.tif

Supplementary material 2 Regional plots of significant Loci associated with serum T3 level. Chromosomes are shown on the x-axis, and the − log10 p value on the y-axis. The color of each SNP spot, ranging from red to blue, reflects the degree of linkage disequilibrium (r2) with between other SNPs and top SNP (purple) (TIF 6976.1 kb)

13258_2021_1165_MOESM3_ESM.tif

Supplementary material 3 Regional plots of significant Loci associated with serum T4 level.  Chromosomes are shown on the x-axis, and the − log10 p value on the y-axis. The color of each SNP spot, ranging from red to blue, reflects the degree of linkage disequilibrium (r2) with between other SNPs and top SNP (purple) (TIF 4876.9 kb)

13258_2021_1165_MOESM4_ESM.tif

Supplementary material 4 Regional plots of significant Loci associated with serum TGA level. Chromosomes are shown on the x-axis, and the − log10 p value on the y-axis. The color of each SNP spot, ranging from red to blue, reflects the degree of linkage disequilibrium (r2) with between other SNPs and top SNP (purple) (TIF 4749.0 kb)

13258_2021_1165_MOESM5_ESM.tif

Supplementary material 5 Regional plots of significant Loci associated with serum TMA level. Chromosomes are shown on the x-axis, and the − log10 p value on the y-axis. The color of each SNP spot, ranging from red to blue, reflects the degree of linkage disequilibrium (r2) with between other SNPs and top SNP (purple) (TIF 4628.3 kb)

13258_2021_1165_MOESM6_ESM.tif

Supplementary material 6 Regional plots of significant Loci associated with serum TSH level. Chromosomes are shown on the x-axis, and the − log10 p value on the y-axis. The color of each SNP spot, ranging from red to blue, reflects the degree of linkage disequilibrium (r2) with between other SNPs and top SNP (purple) (TIF 2230.7 kb)

Supplementary material 7 (DOCX 20.1 kb)

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Huang, L., Bai, F., Zhang, Y. et al. Preliminary study of genome-wide association identified novel susceptibility genes for thyroid-related hormones in Chinese population. Genes Genom 44, 1031–1038 (2022). https://doi.org/10.1007/s13258-021-01165-1

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