ArticleGenes & nutrition2022
Mendelian randomization analysis of vitamin D in the secondary prevention of hypertensive-diabetic subjects: role of facilitating blood pressure control.
Article in Genes & nutrition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Vitamin D and human health: evidence from Mendelian randomization studies.European journal of epidemiology · 2024Pooled it
- Pre-procedural vitamin D deficiency and poor prognosis post-thrombectomy in patients with acute anterior circulation large vessel occlusion: a retrospective cohort study.Frontiers in neurology · 2026Article
- Transforming Alzheimer's Treatment: Unveiling New Potential with Drug Repurposing Strategies.Current medicinal chemistry · 2025Review
- Impact of vitamin D supplementation on cognitive impairment in elderly individuals with hypertension.Frontiers in neurology · 2025Article
- Effect of trace elements and nutrients on diabetes and its complications: a Mendelian randomization study.Frontiers in nutrition · 2024Article
- Health Effects of Vitamin D Supplementation: Lessons Learned From Randomized Controlled Trials and Mendelian Randomization Studies.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Review
- Genotype-informed nutrition counselling in clinical practice.BMJ nutrition, prevention & health · 2023Article
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Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundVitamin D (Vit-D) promotes vascular repair and its deficiency is closely linked to the development of type 2 diabetes mellitus (T2DM) and hypertension. Whether genetially predicted vitamin D status (serological 25-hydroxyvitamin D [25(OH)D]) confers secondary protection against cardiovascular diseases (CVD) among high-risk hypertensive-diabetic subjects was unknown.
methodsThis is a prospective, individual-data, two-sample Mendelian randomization study. We interrogated 12 prior GWAS-detected SNPs of comprehensive Vit-D mechanistic pathways using high-throughput exome chip analyses in a derivation subcohort (n = 1460) and constructed a genetic risk score (GRS) (rs2060793, rs4588, rs7041; F-statistic = 32, P < 0.001) for causal inference of comprehensive CVD hard clinical endpoints in an independent sample of hypertensive subjects (n = 3746) with prevailing co-morbid T2DM (79%) and serological 25(OH)D deficiency [< 20 ng/mL] 45%.
resultsAfter 55.6 ± 28.9 months, 561 (15%) combined CVD events including myocardial infarction, unstable angina, ischemic stroke, congestive heart failure, peripheral vascular disease, and cardiovascular death had occurred. Kaplan-Meier analysis showed that genetically predicted reduced vitamin D status was associated with reduced event-free survival from combined CVD events (log-rank = 13.5, P = 0.001). Multivariate-adjusted per-allele increase in GRS predicted reduced combined CVD events (HR = 0.90 [0.84 to 0.96], P = 0.002). Mendelian randomization indicates that increased Vit-D exposure, leveraged through each 1 ng/mL genetically instrumented rise of serum Vit-D, protects against combined CVD events (Wald's estimate: OR = 0.86 [95%CI 0.75 to 0.95]), and myocardial infarction (OR = 0.76 [95%CI 0.60 to 0.90]). Furthermore, genetically predicted increase in Vit-D status ameliorates risk of deviation from achieving guideline-directed hypertension control (JNC-8: systolic target < 150 mmHg) (OR = 0.89 [95%CI 0.80 to 0.96]).
conclusionsGenetically predicted increase in Vit-D status [25(OH)D] may confer secondary protection against incident combined CVD events and myocardial infarction in a hypertensive-diabetic population where serological 25(OH)D deficiency is common, through facilitating blood pressure control.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.