Circulating Vitamin D Levels and Alzheimer’s Disease: A Mendelian Randomization Study in the IGAP and UK Biobank

Wang, Longcai; Qiao, Yanchun; Zhang, Haihua; Zhang, Yan; Hua, Jing; Jin, Shuilin; Liu, Guiyou

doi:10.3233/jad-190713

Cited by 40 publications

(20 citation statements)

References 39 publications

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“…In MR analyses using the International Genomic of Alzheimer's Project (IGAP) dataset, risk of AD was found to be lower for individuals with genetic variants predicting higher levels of serum 25(OH)D compared to those without these variants [115]. In the most recent analysis using six such alleles (21,982 cases of Alzheimer's disease and 41,944 controls), the relative risk per allele was 0.62 (95% confidence interval 0.46 to 0.84) [115]. Together with the data based on serum levels of 25(OH)D, these findings provide substantial evidence that adequate vitamin D will reduce risk of dementia.…”

Section: Alzheimer's Disease and Dementia And Cognitive Functionmentioning

confidence: 99%

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

2021

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African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer’s disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.

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Section: Alzheimer's Disease and Dementia And Cognitive Functionmentioning

confidence: 99%

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

2021

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“…Using the summary results of these 14 genetic variants in both serum calcium levels and IS GWAS datasets, we first conducted a pleiotropy analysis using two statistical methods including the MR-Egger intercept test and the MR pleiotropy residual sum and outlier (MR-PRESSO) test (Verbanck et al, 2018). Both methods have been widely used in recent MR studies (Liu et al, 2018;Larsson et al, 2019;He et al, 2020;Wang et al, 2020). The statistical significance for evidence of pleiotropy is P < 0.05.…”

Section: Pleiotropy Analysismentioning

confidence: 99%

Integrated Genetics and Micronutrient Data to Inform the Causal Association Between Serum Calcium Levels and Ischemic Stroke

Meng¹,

Huang²,

Tao³

et al. 2020

Front. Cell Dev. Biol.

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There has been an increased interest for observational studies or randomized controlled trials exploring the impact of calcium intake on cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic stroke (IS). However, a direct relationship between total calcium intake and CVD has not been well established and remains controversial. Mendelian randomization (MR) studies have been performed to evaluate the causal association between serum calcium levels and CAD risk and found that increased serum calcium levels could increase the risk of CAD. However, MR analysis found no significant association between genetically higher serum calcium levels and IS as well as its subtypes. Hence, three MR studies reported inconsistent effects of serum calcium levels on CAD and IS. Here, we performed an updated MR study to investigate the association of serum calcium levels with the risk of IS using large-scale genome-wide association study (GWAS) datasets. We selected 14 independent genetic variants as the potential instrumental variables from a large-scale serum calcium GWAS dataset and extracted summary statistics corresponding to the 14 serum calcium genetic variants from the MEGASTROKE Consortium IS GWAS dataset. Interestingly, we found a significant association between serum calcium levels and IS risk using the robust inverse-variance weighted (IVW) and penalized robust IVW methods, with β = 0.243 and P = 0.002. Importantly, the MR results from the robust MR-Egger and penalized robust MR-Egger methods further supported the causal association between serum calcium levels and IS risk, with β = 0.256 and P = 0.005. Meanwhile, the estimates from other MR methods are also consistent with the above findings.

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“…1, a flow chart about our MR study design. The second and third assumptions are collectively known as independence from pleiotropy, as described in recent studies [16][17][18].…”

Section: Methodsmentioning

confidence: 99%

Effect of plasma vitamin C levels on Parkinson’s disease and age at onset: a Mendelian randomization study

Liu

Zhang

et al. 2021

J Transl Med

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Background Until now, epidemiological evidence regarding the association between vitamin C intake (both diet and supplements) and Parkinson’s disease (PD) remains inconsistent. Hence, it is necessary to establish the causal link between vitamin C levels and PD, and further develop effective therapies or prevention. Methods We selected 11 newly identified plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (n = 52,018) as the effective instrumental variables, and extracted their corresponding GWAS summary statistics from PD (33,674 PD cases and 449,056 controls) and PD age at onset (AAO) (n = 28,568). We then performed a Mendelian randomization (MR) study to evaluate the causal association of plasma vitamin C levels with PD and PD AAO using inverse-variance weighted (IVW), the weighted median, MR-Egger, and MR-PRESSO test. Results We did not observe any significant association between genetically increased vitamin C levels and PD. Interestingly, we found a reduced trend of PD AAO (1.134 years) with 1 SD genetically increased vitamin C levels using IVW (beta = − 1.134, 95% CI: [− 2.515, 0.248], P = 0.108). Importantly, this trend was further successfully verified using both weighted median and MR-Egger. Each 1 SD genetically increased vitamin C levels could reduce PD AAO 1.75 and 2.592 years using weighted median (beta = − 1.750, 95% CI: [− 3.396, − 0.105], P = 0.037) and MR-Egger (beta = − 2.592, 95% CI: [− 4.623, − 0.560], P = 0.012). Conclusions We demonstrated the causal association between genetically increased plasma vitamin C levels and reduced PD AAO in people of European descent. Randomized controlled trials are required to clarify whether diet intake or supplement, or both could reduce the AAO of PD.

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Circulating Vitamin D Levels and Alzheimer’s Disease: A Mendelian Randomization Study in the IGAP and UK Biobank

Cited by 40 publications

References 39 publications

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

Integrated Genetics and Micronutrient Data to Inform the Causal Association Between Serum Calcium Levels and Ischemic Stroke

Effect of plasma vitamin C levels on Parkinson’s disease and age at onset: a Mendelian randomization study

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