A mendelian randomization study on causal effects of 25(OH)vitamin D levels on attention deficit/hyperactivity disorder
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ORIGINAL CONTRIBUTION
A mendelian randomization study on causal effects of 25(OH)vitamin D levels on attention deficit/hyperactivity disorder Lars Libuda1,2 · Roaa Naaresh1 · Christine Ludwig1 · Björn‑Hergen Laabs3 · Jochen Antel1 · Manuel Föcker4 · Johannes Hebebrand1 · Anke Hinney1 · Triinu Peters1 Received: 31 March 2020 / Accepted: 4 November 2020 © The Author(s) 2020
Abstract 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 Vitamin D · 25(OH)vitamin D · ADHD · Attention · Mendelian randomization · Prevention
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00394-020-02439-2) contains supplementary material, which is available to authorized users. * Lars Libuda lars.libuda@uni‑due.de 1
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Virchowstr. 174, 45147 Essen, Germany
2
Research Institute for the Prevention of Allergies and Respiratory Diseases in Childhood, Department of Pediatrics, Marien-Hospital Wesel, 46483 Wesel, Germany
3
Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, 23562 Lübeck, Germany
4
Department of Child and Adolescent Psychiatry, University of Münster, 48149 Münster, Germany
Considering its impact on calcium and phosphate metabolism, vitamin D had initially been discussed in particular in the context of bone health [1]. While European scientific societies already recommend vitamin D supplementation during infancy [2], recent findings from observational studies on potential negative non-skeletal effec
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