Dataset Information

Bidirectional Mendelian Randomization Analysis for Vitamin D and Thyroid Peroxidase Antibody.

ABSTRACT:

Purpose

Whether Vitamin D deficiency or insufficiency is associated with thyroid autoimmunity was debated for long time. This study was still to explore the causal relationship of 25 (OH) D with a thyroid peroxidase antibody (TPOAb).

Methods

The data were obtained from a cross-sectional study, SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. 10636 participants were finally included in this study. Genotyped four 25 (OH) D-related and four TPOAb-associated single nucleotide polymorphisms (SNPs) created their genetic risk scores (GRS). Bidirectional mendelian randomization (MR) analysis was used in this study.

Results

25 (OH) D GRS was significantly associated with 25 (OH) D (B -0.093, 95% CI -0.111, -0.074) and TPOAb level (B 0.067, 95% CI 0.002 to 0.132). TPOAb GRS was significantly associated with TPOAb concentration (B 0.345, 95% CI 0.135 to 0.556), but not 25 (OH) D (B -0.030, 95% CI -0.091 to 0.030). Using 25 (OH) D_GRS as instrumental variable in the MR analysis, a causal relationship of genetically determined 25 (OH) D with increased TPOAb concentration (B -0.720, 95% CI -1.429 to -0.012). No relation was found between genetically instrumented TPOAb and 25 (OH) D.

Conclusion

A higher VD_GRS was associated with higher risk of increased TPOAb concentration, which supports a causal association between decreased vitamin D and increased concentration of TPOAb in an eastern Chinese population.

SUBMITTER: Chen Y

PROVIDER: S-EPMC8993571 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Bidirectional Mendelian Randomization Analysis for Vitamin D and Thyroid Peroxidase Antibody.

Chen Yingchao Y Han Bing B Zhu Chunfang C Li Qin Q Chen Chi C Zhai Hualing H Wang Ningjian N Chen Yi Y Lu Yingli Y

International journal of endocrinology 20220401

<h4>Purpose</h4>Whether Vitamin D deficiency or insufficiency is associated with thyroid autoimmunity was debated for long time. This study was still to explore the causal relationship of 25 (OH) D with a thyroid peroxidase antibody (TPOAb).<h4>Methods</h4>The data were obtained from a cross-sectional study, SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. 10636 participants were finally included in this study. Genotyped four 25 (OH) D-related and four TPOAb- ...[more]

PMID: 35399300

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Project description:BackgroundNumerous organs, including the thyroid gland, depend on vitamin D to function normally. Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] are seen as a potential factor contributing to the emergence of several thyroid disorders, however, the causal relationship remains unclear. Here we use a Mendelian randomization (MR) approach to investigate the causal effect of serum 25(OH)D concentration on the indicators of thyroid function.MethodsWe conducted a two-sample MR analysis utilizing summary data from the most extensive genome-wide association studies (GWAS) of serum 25(OH)D concentration (n = 443,734 and 417,580), thyroid-stimulating hormone (TSH, n = 271,040), free thyroxine (fT4, n = 119,120), free triiodothyronine (fT3, n = 59,061), total triiodothyronine (TT3, n = 15,829), as well as thyroid peroxidase antibody levels and positivity (TPOAb, n = 12,353 and n = 18,297), low TSH (n = 153,241), high TSH (n = 141,549), autoimmune hypothyroidism (n = 287,247) and autoimmune hyperthyroidism (n = 257,552). The primary analysis was conducted using the multiplicative random-effects inverse variance weighted (IVW) method. The weighted mode, weighted median, MR-Egger, MR-PRESSO, and Causal Analysis Using Summary Effect estimates (CAUSE) were used in the sensitivity analysis.ResultsThe IVW, as well as MR Egger and CAUSE analysis, showed a suggestive causal effect of 25(OH)D concentration on high TSH. Each 1 SD increase in serum 25(OH)D concentration was associated with a 12% decrease in the risk of high TSH (p = 0.02). Additionally, in the MR Egger and CAUSE analysis, we found a suggestive causal effect of 25(OH)D concentration on autoimmune hypothyroidism. Specifically, each 1 SD increase in serum 25(OH)D concentration was associated with a 16.34% decrease in the risk of autoimmune hypothyroidism (p = 0.02).ConclusionsOur results support a suggestive causal effect which was negative in direction across all methods used, meaning that higher genetically predicted vitamin D concentration possibly lowers the odds of having high TSH or autoimmune hypothyroidism. Other thyroid parameters were not causally influenced by vitamin D serum concentration.

Project description:PurposeThis study aimed to assess the causal relationships between vitamin D levels and ocular disorders.MethodsIndependent genetic variables were obtained from genome-wide association studies (GWAS) and publicly available databases. The summary statistics for 25-hydroxyvitamin D (25(OH)D) were obtained from two large-scale GWAS studies, with sample sizes of 324,105 and 417,580 European individuals. The genetic variants of myopia, primary open angle glaucoma (POAG), anterior iridocyclitis, senile cataract, diabetic retinopathy (DR), retinal vein occlusion (RVO), wet age-related macular degeneration (WAMD) and optic neuritis were extracted from the latest release of FinnGen consortium, which contains genome data from Finnish participants. Subsequently, Mendelian randomization (MR) analyses were conducted to obtain effect estimates. Additionally, we performed multivariable MR analysis and mediation analysis to validate the results.ResultsIn the discovery dataset, genetically predicted vitamin D concentration was found to be causally associated with an increased risk of WAMD, (odd ratio (OR) = 1.35, 95% confidence interval (CI) = 1.09-1.67, P IVW = 0.005). However, no causal effects of genetically predisposed vitamin D levels on the risk of most types of ocular disorders were observed. Reverse MR revealed no causal relationships between the ocular diseases and vitamin D concentrations. The MR analyses of the validation dataset yielded consistent results. Additionally, the causal effect of vitamin D levels on the risk of WAMD remained significant after adjusting for potential confounders in the multivariable MR analysis (OR = 1.86, 95% CI = 1.26-2.73, P IVW = 0.002).ConclusionOur MR analysis results provide robust evidence of a causal relationship between genetically predicted 25(OH)D levels and an increased risk of WAMD in European population. These findings offer important insights into the management and control of ocular disorders.

Dataset Information

Bidirectional Mendelian Randomization Analysis for Vitamin D and Thyroid Peroxidase Antibody.

Purpose

Methods

Results

Conclusion

Publications

Bidirectional Mendelian Randomization Analysis for Vitamin D and Thyroid Peroxidase Antibody.

Similar Datasets

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