| Title: | Vitamin D levels and risk of delirium: A mendelian randomization study in the UK Biobank |
| Journal: | Neurology |
| Published: | 15 Feb 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30770424/ |
| DOI: | https://doi.org/10.1212/wnl.0000000000007136 |
| URL: | https://n.neurology.org/content/neurology/92/12/e1387.full.pdf |
Publication 5994
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Abstract
OBJECTIVE: To estimate effects of vitamin D levels on incident delirium hospital admissions using inherited genetic variants in mendelian randomization models, which minimize confounding and exclude reverse causation.</p>
METHODS: Longitudinal analysis using the UK Biobank, community-based, volunteer cohort (2006-2010) with incident hospital-diagnosed delirium (ICD-10 F05) ascertained during ≤9.9 years of follow-up of hospitalization records (to early 2016). We included volunteers of European descent aged 60-plus years by end of follow-up. We used single-nucleotide polymorphisms previously shown to increase circulating vitamin D levels, and APOE variants. Cox competing models accounting for mortality were used.</p>
RESULTS: Of 313,121 participants included, 544 were hospitalized with delirium during follow-up. Vitamin D variants were protective for incident delirium: hazard ratio = 0.74 per 10 nmol/L (95% confidence interval 0.62-0.87, p = 0.0004) increase in genetically instrumented vitamin D, with no evidence for pleiotropy (mendelian randomization-Egger p > 0.05). Participants with ≥1 APOE ε4 allele were more likely to develop delirium (e.g., ε4ε4 hazard ratio = 3.73, 95% confidence interval 2.68-5.21, p = 8.0 × 10-15 compared to ε3ε3), but there was no interaction with vitamin D variants.</p>
CONCLUSIONS AND RELEVANCE: In a large community-based cohort, there is genetic evidence supporting a causal role for vitamin D levels in incident delirium. Trials of correction of low vitamin D levels in the prevention of delirium are needed.</p>
17 Keywords
- Adult
- Aged
- Apolipoproteins E
- Biological Specimen Banks
- Delirium
- Female
- Follow-Up Studies
- Humans
- Longitudinal Studies
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Polymorphism, Single Nucleotide
- Prospective Studies
- United Kingdom
- Vitamin D
- White People
8 Authors
- Kirsty Bowman
- Lindsay Jones
- Luke C Pilling
- João Delgado
- George A Kuchel
- Luigi Ferrucci
- Richard H Fortinsky
- David Melzer
1 Application
| Application ID | Title |
|---|---|
| 14631 | Genetic and environmental influences on ageing well |
Enabling scientific discoveries that improve human health