No Causal Association between 25-Hydroxyvitamin D and Features of Skin Aging: Evidence from a Bidirectional Mendelian Randomization Study

Background In observational studies, 25 hydroxyvitamin D (25OHD) concentration has been associated with an increased risk of Coronavirus disease 2019 (COVID-19). However, it remains unclear whether this association is causal. Methods We performed a two-sample Mendelian randomization (MR) to explore the causal relationship between 25OHD concentration and COVID-19, using summary data from the genome-wide association studies (GWASs) and using 25OHD concentration-related SNPs as instrumental variables (IVs). Results MR analysis did not show any evidence of a causal association of 25OHD concentration with COVID-19 susceptibility and severity (odds ratio [OR]=1.136, 95% confidence interval [CI] 0.988-1.306, P=0.074; OR=0.889, 95% CI 0.549-1.439, P=0.632). Sensitivity analyses using different instruments and statistical models yielded similar findings, suggesting the robustness of the causal association. No obvious pleiotropy bias and heterogeneity were observed. Conclusion The MR analysis showed that there might be no linear causal relationship of 25OHD concentration with COVID-19 susceptibility and severity.

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Mendelian randomization study updates the effect of 25-hydroxyvitamin D levels on the risk of multiple sclerosis

Journal of Translational Medicine ◽

10.1186/s12967-021-03205-6 ◽

2022 ◽

Vol 20 (1) ◽

Author(s):

Renxi Wang

Keyword(s):

Multiple Sclerosis ◽

Large Scale ◽

Mendelian Randomization ◽

European Ancestry ◽

Causal Association ◽

Serum 25Ohd ◽

Hydroxyvitamin D ◽

Simple Mode ◽

Weighted Median ◽

25 Hydroxyvitamin D

Abstract Background Observational studies and previous Mendelian randomization (MR) studies have shown that genetically low 25-hydroxyvitamin D (25OHD) levels are associated with a high susceptibility to multiple sclerosis (MS). The present MR study aims to update the causal estimates for the effects of 25OHD levels on MS risk. Methods To date, the largest genome-wide association study (GWAS) for serum 25OHD (n = 401,460) and MS (14,498 MS cases and 24,091 controls) was used to assess the effect of serum 25OHD levels on MS. All participants were of European ancestry. The MR-egger_intercept test and Cochran’s Q statistic were used to determine the pleiotropy and the heterogeneity, respectively. MR-egger, weighted median, inverse variance weighted (multiplicative random effects), simple mode, and weighted mode methods were used to evaluate the causal association of serum 25OHD levels with MS. Finally, the effect of a single 25OHD SNP (single nucleotide polymorphism) on MS was used to test the SNP bias. Results One hundred and fifteen newly identified serum 25OHD genetic variants were extracted from a large-scale serum 25OHD GWAS dataset. The 20 most effective and independent 25OHD genetic instrumental variables were extracted from the MS GWAS summary statistics. Pleiotropy analysis suggested no significant pleiotropic variant among the 20 selected 25OHD genetic instrument variants in MS GWAS datasets. As serum levels of 25OHD based on genetic changes increased, the risk of MS decreased using MR-egger (Beta = − 0.940, p = 0.001; OR = 0.391), weighted median (Beta = − 0.835, p = 0.000; OR = 0.434), IVW (Beta = − 0.781, p = 0.000; OR = 0.458), simple mode (Beta = − 1.484, p = 0.016; OR = 0.227), and weighted mode (Beta = − 0.913, p = 0.000; OR = 0.401). Our results were robust, with no obvious bias based on investigating the single 25OHD SNP on MS. Conclusions Our analysis suggested a causal association between genetically increased serum 25OHD levels and reduced MS in the European population.

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The Impact of Serum 25-hydroxyvitamin D, Calcium, and Parathyroid Hormone Levels on the Risk of Coronary Artery Disease in Patients With Diabetes: A Mendelian Randomization Study

10.21203/rs.3.rs-97969/v1 ◽

2020 ◽

Author(s):

Songzan Chen ◽

Fangkun Yang ◽

Tian Xu ◽

Yao Wang ◽

Kaijie Zhang ◽

...

Keyword(s):

Coronary Artery Disease ◽

Parathyroid Hormone ◽

Coronary Artery ◽

Mendelian Randomization ◽

Causal Association ◽

Serum 25Ohd ◽

Hydroxyvitamin D ◽

Patients With Diabetes ◽

25 Hydroxyvitamin D ◽

Artery Disease

Abstract BackgroundTo investigate the causal association between serum 25-hydroxyvitamin D (25OHD), calcium (Ca), and parathyroid hormone (PTH) levels and the risk of coronary artery disease (CAD) in patients with diabetes using a Mendelian randomization approach.MethodsGenetic signatures associated with serum 25OHD, Ca, and PTH levels were extracted from recently published genome-wide association study (GWAS), including 79,366, 39,400, 29,155 individuals, respectively. Genetic association estimates for CAD in patients with diabetes were obtained from a GWAS of 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The inverse-variance-weighted method was employed for the primary analysis, and other robust methods were applied for sensitivity analyses.ResultsSix, seven and five single nucleotide polymorphisms were identified as instrumental variables for serum 25OHD, Ca and PTH levels, respectively. There was no significant association between genetically predicted serum 25OHD levels and the risk of CAD in patients with diabetes (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.58 - 1.87, P = 0.888). Similarly, genetically predicted serum Ca (OR = 1.83, 95% CI: 0.62 – 5.35, P = 0.273) and PTH levels (OR = 1.27, 95% CI: 0.67 – 2.44, P = 0.464) were not significantly associated with the risk of CAD in patients with diabetes. These findings were robust in sensitivity analyses.Conclusions/interpretationThis study found no evidence to support the causal association between serum 25OHD, Ca and PTH levels and the risk of CAD in patients with diabetes.

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Association of 25 Hydroxyvitamin D Concentration with Risk of COVID-19: A Mendelian Randomization Study

10.21203/rs.3.rs-68830/v1 ◽

2020 ◽

Author(s):

Di Liu ◽

Qiuyue Tian ◽

Jie Zhang ◽

Haifeng Hou ◽

Wei Wang ◽

...

Keyword(s):

Causal Relationship ◽

Mendelian Randomization ◽

Association Studies ◽

Sensitivity Analyses ◽

Genome Wide Association Studies ◽

Causal Association ◽

Hydroxyvitamin D ◽

Increased Risk ◽

25Ohd Concentration ◽

25 Hydroxyvitamin D

Abstract Background: Coronavirus disease 2019 (COVID-19) has caused a large global pandemic. In observational studies, 25 hydroxyvitamin D (25OHD) concentration has been associated with an increased risk of Coronavirus disease 2019 (COVID-19). However, it remains unclear whether this association is causal.Methods: We performed a two-sample Mendelian randomization (MR) to explore the causal relationship between 25OHD concentration and COVID-19, using summary data from the genome-wide association studies (GWASs) and using 25OHD concentration-related SNPs as instrumental variables (IVs). Results: MR analysis did not show any evidence of a causal association of 25OHD concentration with COVID-19 susceptibility and severity (odds ratio [OR]=1.136, 95% confidence interval [CI] 0.988-1.306, P=0.074; OR=0.889, 95% CI 0.549-1.439, P=0.632). Sensitivity analyses using different instruments and statistical models yielded similar findings, suggesting the robustness of the causal association. No obvious pleiotropy bias and heterogeneity were observed.Conclusions: The MR analysis showed that there might be no linear causal relationship of 25OHD concentration with COVID-19 susceptibility and severity.

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Assessing the causal association between 25-hydroxyvitamin D and the risk of oral and oropharyngeal cancer using Mendelian randomization

International Journal of Cancer ◽

10.1002/ijc.31377 ◽

2018 ◽

Vol 143 (5) ◽

pp. 1029-1036 ◽

Cited By ~ 5

Author(s):

Tom Dudding ◽

Mattias Johansson ◽

Steven J. Thomas ◽

Paul Brennan ◽

Richard M. Martin ◽

...

Keyword(s):

Oropharyngeal Cancer ◽

Mendelian Randomization ◽

Causal Association ◽

Hydroxyvitamin D ◽

Oral And Oropharyngeal Cancer ◽

25 Hydroxyvitamin D

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Association of 25-Hydroxyvitamin D with Cardiometabolic Risk Factors and Metabolic Syndrome: A Mendelian Randomization Study

SSRN Electronic Journal ◽

10.2139/ssrn.3273664 ◽

2018 ◽

Author(s):

Chi Chen ◽

Yi Chen ◽

Pan Weng ◽

Fangzhen Xia ◽

Qin Li ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Cardiometabolic Risk ◽

Mendelian Randomization ◽

Cardiometabolic Risk Factors ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D

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Association of serum 25-hydroxyvitamin D with metabolic syndrome and type 2 diabetes: a one sample Mendelian randomization study

BMC Geriatrics ◽

10.1186/s12877-021-02307-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jing Xiao ◽

Jingyi Lv ◽

Shiyu Wang ◽

Yang Zhou ◽

Lunwen Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Mendelian Randomization ◽

Middle Aged ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Randomization Analysis

Abstract Background Vitamin D deficiency has been associated with type 2 diabetes (T2D) and metabolic syndrome (MS) and its components. However, it is unclear whether a low concentration of vitamin D is the cause or consequence of these health conditions. Thus, this study aimed to evaluate the association of vitamin D concentrations and its genetic risk scores (GRSs) with MS and its component diseases, such as T2D, in middle-aged and elderly participants from rural eastern China. Methods A subset of 2393 middle-aged and elderly individuals were selected from 70,458 participants of the Nantong Chronic Diseases Study of 2017–2018 in China. We used two 25-hydroxyvitamin D (25[OH]D) synthesis single-nucleotide polymorphisms (SNPs) (DHCR7-rs12785878 and CYP2R1-rs10741657) and two 25(OH) D metabolism SNPs (GC-rs2282679 and CYP24A1-rs6013897) for creating GRSs, which were used as instrumental variables to assess the effect of genetically lowered 25(OH) D concentrations on MS and T2D based on the Wald ratio. F statistics were used to validate that the four SNPs genetically determined 25(OH) D concentrations. Results Compared to vitamin D sufficient individuals, individuals with vitamin D insufficiency had an odds ratio (OR [95% confidence interval {CI}]) of MS of 1.30 (1.06–1.61) and of T2D of 1.32 (1.08–1.64), individuals with vitamin D deficiency had an ORs (95% CI) of MS of 1.50 (1.24–1.79) and of T2D of 1.47 (1.12–1.80), and those with vitamin D severe deficiency had an ORs (95% CI) of MS of 1.52 (1.29–1.85) and of T2D of 1.54 (1.27–1.85). Mendelian randomization analysis showed a 25-nmol/L decrease in genetically instrumented serum 25(OH) D concentrations using the two synthesis SNPs (DHCR7 and CYP2R1 genes) associated with the risk of T2D and abnormal diastolic blood pressure (DBP) with ORs of 1.10 (95%CI: 1.02–1.45) for T2D and 1.14 (95%CI: 1.03–1.43) for DBP. Conclusions This one sample Mendelian randomization analysis shows genetic evidence for a causal role of lower 25(OH) D concentrations in promoting of T2D and abnormal DBP in middle-aged and elderly participants from rural China.

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The impact of serum 25-hydroxyvitamin D, calcium, and parathyroid hormone levels on the risk of coronary artery disease in patients with diabetes: a Mendelian randomization study

Nutrition Journal ◽

10.1186/s12937-021-00735-z ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Songzan Chen ◽

Fangkun Yang ◽

Tian Xu ◽

Yao Wang ◽

Kaijie Zhang ◽

...

Keyword(s):

Coronary Artery Disease ◽

Parathyroid Hormone ◽

Coronary Artery ◽

Mendelian Randomization ◽

Sensitivity Analyses ◽

Serum 25Ohd ◽

Hydroxyvitamin D ◽

Patients With Diabetes ◽

25 Hydroxyvitamin D ◽

Artery Disease

Abstract Background To investigate the causal association between serum 25-hydroxyvitamin D (25OHD), calcium (Ca), and parathyroid hormone (PTH) levels and the risk of coronary artery disease (CAD) in patients with diabetes using a Mendelian randomization approach. Methods Genetic signatures associated with serum 25OHD, Ca, and PTH levels were extracted from recently published genome-wide association study (GWAS), including 79,366, 39,400, 29,155 individuals, respectively. Genetic association estimates for CAD in patients with diabetes were obtained from a GWAS of 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The inverse-variance-weighted method was employed for the primary analysis, and other robust methods were applied for sensitivity analyses. Results Six, seven and five single nucleotide polymorphisms were identified as instrumental variables for serum 25OHD, Ca and PTH levels, respectively. There was no significant association between genetically predicted serum 25OHD levels and the risk of CAD in patients with diabetes (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.58 - 1.87, P = 0.888). Similarly, genetically predicted serum Ca (OR = 1.83, 95% CI: 0.62 – 5.35, P = 0.273) and PTH levels (OR = 1.27, 95% CI: 0.67 – 2.44, P = 0.464) were not significantly associated with the risk of CAD in patients with diabetes. These findings were robust in sensitivity analyses. Conclusions/interpretation Serum 25OHD, Ca and PTH levels may not be causally associated with the risk of CAD in patients with diabetes.

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