A mendelian randomization study on causal effects of 25(OH)vitamin D levels on attention deficit/hyperactivity disorder

Eur J Nutr. 2021 Aug;60(5):2581-2591. doi: 10.1007/s00394-020-02439-2. Epub 2020 Nov 27.


Background: While observational studies revealed an inverse association between serum 25(OH)vitamin D (25(OH)D) and the risk of attention deficit/hyperactivity disorder (ADHD), the causality of this relationship remains unclear.

Methods: We conducted a bidirectional two-sample Mendelian Randomization (MR) study to examine whether 25(OH)D has an effect on the risk to develop ADHD or vice versa. Information on single nucleotide polymorphisms (SNP) associated with serum 25(OH)D was obtained from a genome-wide association study (GWAS) considering phenotype data from 79,366 individuals of European ancestry. Data on risk for ADHD were derived from a GWAS analysis with 20,183 individuals diagnosed with ADHD and 35,191 controls. For our analysis, we considered effect sizes based on the European participants (19,099 cases and 34,194 controls).

Results: Single SNP analyses showed a causal effect of vitamin D on ADHD risk for only one SNP (rs12785878, p = 0.024). The overall MR estimates did not reveal a causal effect of 25(OH)D on risk for ADHD. In the reverse analysis, neither any single nor the multi-SNP MR analyses showed a causal effect of ADHD on 25(OH)D.

Conclusion: Results from this two-sample MR study did not confirm a causal effect of 25(OH)D on ADHD or vice versa. Accordingly, our study does not provide evidence that improving 25(OH)D via supplementation could reduce the risk of developing ADHD.

Keywords: 25(OH)vitamin D; ADHD; Attention; Mendelian randomization; Prevention; Vitamin D.

MeSH terms

  • Attention Deficit Disorder with Hyperactivity* / genetics
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Polymorphism, Single Nucleotide
  • Vitamin D*


  • Vitamin D