scholarly journals Serum 25-Hydroxyvitamin D Concentrations and Major Depression: A Mendelian Randomization Study

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1987 ◽  
Author(s):  
Karl Michaëlsson ◽  
Håkan Melhus ◽  
Susanna Larsson
Keyword(s):  
Vitamin D ◽  
Major Depression ◽  
Mendelian Randomization ◽  
Vitamin D Insufficiency ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D

Whether vitamin D insufficiency is a contributing cause of depression remains unclear. We assessed whether serum 25-hydroxyvitamin D (S-25OHD) concentrations, the clinical marker of vitamin D status, were associated with major depression using Mendelian randomization. We used summary statistics data for six single-nucleotide polymorphisms significantly associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) consortium and the corresponding data for major depression (n = 59,851 cases and 113,154 controls) from the Psychiatric Genomics Consortium. Genetically predicted S-25OHD concentrations were not associated with major depression. The odds ratio per genetically predicted one standard deviation decrease in S-25OHD concentrations was 1.02 (95% confidence interval 0.97–1.08; p = 0.44). The results of this study indicate that genetically lowered S-25OHD concentrations are not associated with increased risk of developing major depression.

scholarly journals Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D–Related Genetic Variants

2017 ◽  
Vol 102 (8) ◽  
pp. 2941-2949 ◽  
Author(s):  
Rebecca J Moon ◽  
Nicholas C Harvey ◽  
Cyrus Cooper ◽  
Stefania D’Angelo ◽  
Elizabeth M Curtis ◽  
...  
Keyword(s):  
Vitamin D ◽  
Group Analysis ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Vitamin D Metabolism ◽  
Single Nucleotide ◽  
White Ethnicity ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Cholecalciferol Supplementation

Abstract Context Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. Objective To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation. Design Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation. Setting Hospital antenatal clinics. Participants In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped. Interventions 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery. Main Outcome Measure 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele]. Results Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (β = −5.2 nmol/L; 95% CI, −8.2 to −2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not. Conclusions Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.

scholarly journals The relative contributions of obesity, vitamin D, leptin, and adiponectin to multiple sclerosis risk: A Mendelian randomization mediation analysis

2021 ◽  
pp. 135245852199548 ◽  
Author(s):  
Adil Harroud ◽  
Despoina Manousaki ◽  
Guillaume Butler-Laporte ◽  
Ruth E Mitchell ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Mediation Analysis ◽  
Mendelian Randomization ◽  
Vitamin D Supplementation ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
Vitamin D Levels ◽  
25 Hydroxyvitamin D ◽  
Underlying Mechanisms

Background: Obesity is associated with increased risk of multiple sclerosis (MS); however, the underlying mechanisms remain unclear. Objective: To determine the extent to which decreased vitamin D bioavailability and altered levels of adiponectin and leptin mediate the association between obesity and MS. Methods: We performed Mendelian randomization (MR) analyses to estimate the effects on MS of body mass index (BMI), 25-hydroxyvitamin D (25OHD), adiponectin, and leptin levels in a cohort of 14,802 MS cases and 26,703 controls. We then estimated the proportion of the effect of obesity on MS explained by these potential mediators. Results: Genetic predisposition to higher BMI was associated with increased MS risk (odds ratio (OR) = 1.33 per standard deviation (SD), 95% confidence interval (CI) = 1.09–1.63), while higher 25OHD levels reduced odds of MS (OR = 0.72 per SD, 95% CI = 0.60–0.87). In contrast, we observed no effect of adiponectin or leptin. In MR mediation analysis, 5.2% of the association between BMI and MS was attributed to obesity lowering 25OHD levels (95% CI = 0.3%–31.0%). Conclusions: This study found that a minority of the increased risk of MS conferred by obesity is mediated by lowered vitamin D levels, while leptin and adiponectin had no effect. Consequently, vitamin D supplementation would only modestly reverse the effect of obesity on MS.

scholarly journals Associations between Genetic Variants in the Vitamin D Metabolism Pathway and Severity of COVID-19 among UAE Residents

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3680
Author(s):  
Fatme Al-Anouti ◽  
Mira Mousa ◽  
Spyridon N. Karras ◽  
William B. Grant ◽  
Zainab Alhalwachi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
United Arab Emirates ◽  
Genetic Variants ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Potential Risk Factors ◽  
25 Hydroxyvitamin D

Vitamin D has many effects on cells in the immune system. Many studies have linked low vitamin D status with severity of COVID-19. Genetic variants involved in vitamin D metabolism have been implicated as potential risk factors for severe COVID-19 outcomes. This study investigated how genetic variations in humans affected the clinical presentation of COVID-19. In total, 646 patients with SARS-CoV-2 infection were divided into two groups: noncritical COVID-19 (n = 453; 70.12%) and a critical group (n = 193; 29.87%). Genotype data on the GC, NADSYN1, VDR, and CYP2R1 genes along with data on serum 25-hydroxyvitamin D levels were compiled in patients admitted to a major hospital in the United Arab Emirates between April 2020 and January 2021. We identified 12 single-nucleotide polymorphisms associated with the critical COVID-19 condition: rs59241277, rs113574864, rs182901986, rs60349934, and rs113876500; rs4944076, rs4944997, rs4944998, rs4944979, and rs10898210; and rs11574018 and rs11574024. We report significant associations between genetic determinants of vitamin D metabolism and COVID-19 severity in the UAE population. Further research needed to clarify the mechanism of action against viral infection in vitamin D deficiency. These variants could be used with vaccination to manage the spread of SARS-CoV-2 and could be particularly valuable in populations in which vitamin D deficiency is common.

scholarly journals 25-Hydroxyvitamin D and Risk of Osteoporotic Fractures: Mendelian Randomization Analysis in 2 Large Population-Based Cohorts

2020 ◽  
Vol 66 (5) ◽  
pp. 676-685 ◽  
Author(s):  
Yunus Çolak ◽  
Shoaib Afzal ◽  
Børge G Nordestgaard
Keyword(s):  
Vitamin D ◽  
Mendelian Randomization ◽  
Osteoporotic Fractures ◽  
Population Based ◽  
Hydroxyvitamin D ◽  
Mendelian Randomization Analysis ◽  
Hazard Ratios ◽  
Increased Risk ◽  
25 Hydroxyvitamin D ◽  
Randomization Analysis

Abstract Background Whether low plasma 25-hydroxyvitamin D concentrations cause osteoporotic fractures is unclear. We tested the hypothesis that low plasma 25-hydroxyvitamin D concentrations are associated with increased risk of osteoporotic fractures using a Mendelian randomization analysis. Methods We genotyped 116 335 randomly chosen white Danish persons aged 20–100 years in 2 population-based cohort studies for plasma 25-hydroxyvitamin D decreasing genotypes in CYP2R1 (rs117913124 and rs12794714), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458), and HAL (rs3819817); 35 833 had information on plasma 25-hydroxyvitamin D. We assessed risk of total, osteoporotic, and anatomically localized fractures from 1981 through 2017. Information on fractures and vital status was obtained from nationwide registries. Results During up to 36 years of follow-up, we observed 17 820 total fractures, 10 861 osteoporotic fractures, and 3472 fractures of hip or femur. Compared with individuals with 25-hydroxyvitamin D ≥ 50nmol/L, multivariable adjusted hazard ratios (95% CIs) for total fractures were 1.03 (0.97–1.09) for individuals with 25–49.9 nmol/L, 1.19 (1.10–1.28) for individuals with 12.5–24.9 nmol/L, and 1.39 (1.21–1.60) for individuals with 25-hydroxyvitamin D < 12.5 nmol/L. Corresponding hazard ratios were 1.07 (1.00–1.15), 1.25 (1.13–1.37), and 1.49 (1.25–1.77) for osteoporotic fractures and 1.09 (0.98–1.22), 1.37 (1.18–1.57), and 1.41 (1.09–1.81) for fractures of hip or femur, respectively. Hazard ratios per 1 increase in vitamin D allele score, corresponding to 3.0% (approximately 1.6 nmol/L) lower 25-hydroxyvitamin D concentrations, were 0.99 (0.98–1.00) for total fractures, 0.99 (0.97–1.00) for osteoporotic fractures, and 0.98 (0.95–1.00) for fractures of hip or femur. Conclusions Low plasma 25-hydroxyvitamin D concentrations were associated with osteoporotic fractures; however, Mendelian randomization analysis provided no evidence supporting a causal role for vitamin D in the risk for osteoporotic fractures.

scholarly journals The Associations of Novel Vitamin D3Metabolic GeneCYP27A1Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Kai-Hung Cheng ◽  
Edward Hsi ◽  
Chia-Chu Liu ◽  
Chun-Nung Huang ◽  
Yung-Chin Lee ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Vitamin D ◽  
Hapmap Project ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Preclinical Stage ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
The Individual

Metabolic syndrome (MetS) confers increased risks of cardiovascular disease (CVD). Both vitamin D3and adipocytokines (especially adiponectin and leptin) have a great impact on CVD and MetS. In vitamin D3metabolism, the vitamin D325-hydroxylase (CYP27A1) and 25-hydroxyvitamin D31-alpha-hydroxylase (CYP27B1) are two key enzymes. This study aimed to examine the influence of vitamin D3CYP27 single nucleotide polymorphisms (SNPs) on adipocytokines and MetS. Cross-sectional data and DNA samples were collected from male volunteers (n=649, age: 55.7 ± 4.7 years). Two tagging SNPs,CYP27A1 rs4674344andCYP27B1 rs10877012, were selected from the HapMap project. MetS was significantly associated with theCYP27A1 rs4674344SNP(P=0.04)and the ratio of adiponectin/leptin (A/L ratio) was most correlated to theCYP27A1 rs4674344SNP, appearing to be significantly lower in T-carriers than in AA subjects (3.7 ± 4.0 versus 5.1 ± 6.0,P=0.001) and significantly negatively associated after adjustment. For each MetS component associated with theCYP27A1 rs4674344SNP, the A/L ratios were significantly negative in preclinical stage (condition not meeting the individual criteria), except the blood pressure. In conclusion,CYP27A1 rs4674344SNP, A/L ratio, and MetS are significantly associated and T-carriers might have a higher risk of developing MetS due to low A/L ratios in the preclinical stage.

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

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.

scholarly journals Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden

2010 ◽  
Vol 95 (6) ◽  
pp. 2637-2645 ◽  
Author(s):  
Håkan Melhus ◽  
Greta Snellman ◽  
Rolf Gedeborg ◽  
Liisa Byberg ◽  
Lars Berglund ◽  
...  
Keyword(s):  
Vitamin D ◽  
Uv Light ◽  
Winter Season ◽  
Community Dwelling ◽  
Reference Level ◽  
Blood Levels ◽  
Elderly Men ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D

Abstract Context: Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. Objective: The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. Design and Participants: In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. Setting: The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. Main Outcome Measure: Time to fracture was measured. Results: During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09–2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. Conclusions: Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60°, only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

scholarly journals COVID-19 Disease Severity and Death in Relation to Vitamin D Status among SARS-CoV-2-Positive UAE Residents

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1714
Author(s):  
Habiba AlSafar ◽  
William B. Grant ◽  
Rafiq Hijazi ◽  
Maimunah Uddin ◽  
Nawal Alkaabi ◽  
...  
Keyword(s):  
Vitamin D ◽  
United Arab Emirates ◽  
Blood Levels ◽  
Vitamin D Status ◽  
Hospital Visit ◽  
Serum Samples ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
Multiethnic Population ◽  
25 Hydroxyvitamin D

Insufficient blood levels of the neurohormone vitamin D are associated with increased risk of COVID-19 severity and mortality. Despite the global rollout of vaccinations and promising preliminary results, the focus remains on additional preventive measures to manage COVID-19. Results conflict on vitamin D’s plausible role in preventing and treating COVID-19. We examined the relation between vitamin D status and COVID-19 severity and mortality among the multiethnic population of the United Arab Emirates. Our observational study used data for 522 participants who tested positive for SARS-CoV-2 at one of the main hospitals in Abu Dhabi and Dubai. Only 464 of those patients were included for data analysis. Demographic and clinical data were retrospectively analyzed. Serum samples immediately drawn at the first hospital visit were used to measure serum 25-hydroxyvitamin D [25(OH)D] concentrations through automated electrochemiluminescence. Levels < 12 ng/mL were significantly associated with higher risk of severe COVID-19 infection and of death. Age was the only other independent risk factor, whereas comorbidities and smoking did not contribute to the outcomes upon adjustment. Sex of patients was not an important predictor for severity or death. Our study is the first conducted in the UAE to measure 25(OH)D levels in SARS-CoV-2-positive patients and confirm the association of levels < 12 ng/mL with COVID-19 severity and mortality.

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