Dataset Information

The Effects of Common Genetic Variation in 96 Genes Involved in Thyroid Hormone Regulation on TSH and FT4 Concentrations.

ABSTRACT:

Objective

While most of the variation in thyroid function is determined by genetic factors, single nucleotide polymorphisms (SNPs) identified via genome-wide association analyses have only explained ~5% to 9% of this variance so far. Most SNPs were in or nearby genes with no known role in thyroid hormone (TH) regulation. Therefore, we performed a large-scale candidate gene study investigating the effect of common genetic variation in established TH regulating genes on serum thyrotropin [thyroid-stimulating hormone (TSH)] and thyroxine (FT4) concentrations.

Methods

SNPs in or within 10 kb of 96 TH regulating genes were included (30 031 TSH SNPs, and 29 962 FT4 SNPs). Associations were studied in 54 288 individuals from the ThyroidOmics Consortium. Linkage disequilibrium-based clumping was used to identify independently associated SNPs. SNP-based explained variances were calculated using SumHer software.

Results

We identified 23 novel TSH-associated SNPs in predominantly hypothalamic-pituitary-thyroid axis genes and 25 novel FT4-associated SNPs in mainly peripheral metabolism and transport genes. Genome-wide SNP variation explained ~21% (SD 1.7) of the total variation in both TSH and FT4 concentrations, whereas SNPs in the 96 TH regulating genes explained 1.9% to 2.6% (SD 0.4).

Conclusion

Here we report the largest candidate gene analysis on thyroid function, resulting in a substantial increase in the number of genetic variants determining TSH and FT4 concentrations. Interestingly, these candidate gene SNPs explain only a minor part of the variation in TSH and FT4 concentrations, which substantiates the need for large genetic studies including common and rare variants to unravel novel, yet unknown, pathways in TH regulation.

SUBMITTER: Sterenborg RBTM

PROVIDER: S-EPMC9315164 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

The Effects of Common Genetic Variation in 96 Genes Involved in Thyroid Hormone Regulation on TSH and FT4 Concentrations.

Sterenborg Rosalie B T M RBTM Galesloot Tessel E TE Teumer Alexander A Netea-Maier Romana T RT Speed Doug D Meima Marcel E ME Visser W Edward WE Smit Johannes W A JWA Peeters Robin P RP Medici Marco M

The Journal of clinical endocrinology and metabolism 20220501 6

<h4>Objective</h4>While most of the variation in thyroid function is determined by genetic factors, single nucleotide polymorphisms (SNPs) identified via genome-wide association analyses have only explained ~5% to 9% of this variance so far. Most SNPs were in or nearby genes with no known role in thyroid hormone (TH) regulation. Therefore, we performed a large-scale candidate gene study investigating the effect of common genetic variation in established TH regulating genes on serum thyrotropin [ ...[more]

PMID: 35262175

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Project description:Background: Serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) change dynamically during pregnancy. Differences in geographic regions, populations, and manufacturer's methodologies can affect the reference intervals for thyroid function tests. The 2017 guidelines of the American Thyroid Association (ATA) recommended 4.0 mU/L as the cut-off point for the upper limit of serum TSH in early pregnancy. A systematic review is called for to establish practical, gestational-specific TSH and FT4 reference intervals for pregnant Chinese women and to explore whether the criteria are suitable for China. Methods: English and Chinese articles published from inception to Aug 2017 were searched in the PubMed, EMBASE, and SCIE English-language databases and the CNKI, WanFang, and CQVIP Chinese databases. The relative descent or ascent rates of serum TSH and FT4 were calculated, after which Comprehensive Meta-Analysis V2.0 software was used to analyze the data. Results: Eleven studies (6 in English and 5 in Chinese), five kits and 11,629 Chinese women from nine cities were considered in this meta-analysis. Compared with the reference ranges provided by manufacturers, serum TSH decreased in the first trimester, with the upper limit declining by 21.7% (5.0-36.6%), to a value close to 4.0 mU/L, and the lower limit declining by 85.7% (73.5-97.1%). It continued decreasing in the second trimester, with the upper limit declining by 24.0% (6.4-40.9%) and the lower limit declining by 40.7% (9.0-85.7%). For FT4, the upper limit fluctuated slightly, and the lower limit increased by 6.8% (1.0-14.6%) in the first trimester. Serum FT4 dropped gradually, with the upper limit declining by 21.8% (2.5-31.8%) and the lower limit declining by 12.7% (2.6-19.6%) in the second trimester. During the third trimester, the upper limit decreased by 25.1% (12.7-35.0%), while the lower limit decreased by 20.9% (14.8-27.3%). Conclusions: Various regions, kits and test methods affect the gestational TSH and FT4 levels. The non-pregnant serum TSH upper limit minus 22% is very close to 4.0 mU/L, which can be used as a sub-optimal approach to represent the cut-off value for pregnant Chinese women in the first trimester.

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Dataset Information

The Effects of Common Genetic Variation in 96 Genes Involved in Thyroid Hormone Regulation on TSH and FT4 Concentrations.

Objective

Methods

Results

Conclusion

Publications

The Effects of Common Genetic Variation in 96 Genes Involved in Thyroid Hormone Regulation on TSH and FT4 Concentrations.

Similar Datasets

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