Vitamin D levels and risk of delirium: A mendelian randomization study in the UK Biobank

Neurology. 2019 Mar 19;92(12):e1387-e1394. doi: 10.1212/WNL.0000000000007136. Epub 2019 Feb 15.


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.

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.

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.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoproteins E / genetics
  • Biological Specimen Banks
  • Delirium / epidemiology*
  • Delirium / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Mendelian Randomization Analysis
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • United Kingdom
  • Vitamin D / genetics*
  • White People / genetics


  • Apolipoproteins E
  • Vitamin D