Dataset Information

The causal effect of serum 25-hydroxyvitamin D levels on epilepsy: A two-sample Mendelian randomization study.

ABSTRACT:

Objective

Observational studies have shown an association between 25-hydroxyvitamin D (25 (OH) D) and epilepsy, but it is unclear whether the association is causal. Therefore, we applied Mendelian randomization (MR) analysis to determine the causal relationship between serum 25 (OH) D levels and epilepsy.

Methods

We conducted a two-sample Mendelian randomization (TSMR) study to investigate the association between serum 25 (OH) D levels and epilepsy using pooled statistics from genome-wide association studies (GWAS). Data for 25 (OH) D came from a GWAS comprising 417,580 participants, and data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium. Five methods were used to analyze TSMR, including the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In the sensitivity analysis, MR Egger and MR PRESSO methods were used to test for pleiotropy, inverse variance weighting and MR Egger in Cochran's Q statistics were used to test for heterogeneity.

Results

MR analyzed the relationship between 25 (OH) D and different types of epilepsy, and the results showed that a 1 standard deviation increase in natural log-transformed serum 25 (OH) D levels was associated with reduced risk for juvenile absence epilepsy (IVW OR = 0.985; 95% confidence interval [CI]: 0.971-0.999; P-value = 0.038). There was no apparent heterogeneity and horizontal gene pleiotropy.

Significance

Higher serum levels of 25 (OH) D were a protective factor for adolescent absence epilepsy, but had no effect on other types of epilepsy.

SUBMITTER: Luo X

PROVIDER: S-EPMC10472413 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

The causal effect of serum 25-hydroxyvitamin D levels on epilepsy: A two-sample Mendelian randomization study.

Luo Xinxin X Ruan Zhichao Z Liu Ling L

Epilepsia open 20230515 3

<h4>Objective</h4>Observational studies have shown an association between 25-hydroxyvitamin D (25 (OH) D) and epilepsy, but it is unclear whether the association is causal. Therefore, we applied Mendelian randomization (MR) analysis to determine the causal relationship between serum 25 (OH) D levels and epilepsy.<h4>Methods</h4>We conducted a two-sample Mendelian randomization (TSMR) study to investigate the association between serum 25 (OH) D levels and epilepsy using pooled statistics from gen ...[more]

PMID: 37158995

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Project description:ImportanceVitamin D deficiency is commonly associated with sarcopenia; however, the latest International Clinical Practice Guidelines for Sarcopenia do not recommend vitamin D supplementation for sarcopenia owing to a lack of an apparent therapeutic effect on the indices of sarcopenia among participants with replete vitamin D concentration (ie, 25-hydroxyvitamin D [25(OH)D] level >20 ng/mL) from randomized clinical trials. While there is consensus in all vitamin D guidelines that serum levels of 25(OH)D less than 10 ng/mL should be corrected, approximately 30% of the world population's 25(OH)D levels range from 10 to 20 ng/mL, and it remains unclear whether such suboptimal levels can maintain optimal health, including sarcopenia risk.ObjectiveTo investigate the association of serum 25(OH)D level, especially suboptimal levels, with sarcopenia risk.Design, setting, and participantsThis genome-wide genetic association study was performed from August 2022 to February 2023 among the 295 489 unrelated European participants from the UK Biobank (2006-2010). Nonlinear and standard mendelian randomization analyses were used to examine the association of serum 25(OH)D concentration with sarcopenia risk.ExposuresA weighted genetic risk score using 35 unrelated single-nucleotide variants from the UK Biobank and weights from the SUNLIGHT Consortium was selected as an instrumental variable for serum 25(OH)D concentration.Main outcomes and measuresThe primary outcome was sarcopenia, and the secondary outcomes consisted of grip strength, appendicular lean mass index, and gait speed.ResultsThe final genetic analyses included 295 489 participants (mean [SD] age, 56.3 [8.1] years; 139 216 female [52.9%]). There was an L-shaped association between genetically predicted serum 25(OH)D concentration and sarcopenia risk. The risk of sarcopenia decreased rapidly as 25(OH)D concentration increased until 20 ng/mL and then leveled off. The odds ratio of sarcopenia for serum 25(OH)D level of 10 vs 20 ng/mL was 1.74 (95% CI, 1.17-2.59). Similar patterns were also observed when the association between serum 25(OH)D concentration and risks of each of the sarcopenia indices were evaluated.Conclusions and relevanceIn this mendelian randomization genetic association study of adults in the UK Biobank, the findings supported a nonlinear association between suboptimal 25(OH)D levels and sarcopenia risk. Randomized clinical trials among participants with suboptimal 25(OH)D levels are required to verify the potential causality.

Dataset Information

The causal effect of serum 25-hydroxyvitamin D levels on epilepsy: A two-sample Mendelian randomization study.

Objective

Methods

Results

Significance

Publications

The causal effect of serum 25-hydroxyvitamin D levels on epilepsy: A two-sample Mendelian randomization study.

Similar Datasets

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