Relationship between Serum 25(OH)D and Depression: Causal Evidence from a Bi-Directional Mendelian Randomization Study
1
Australian Centre for Precision Health, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, SA 5000, Australia
2
Department of Pharmacology and Clinical Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa 1000, Ethiopia
3
South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
4
Unit of Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia
5
Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
*
Author to whom correspondence should be addressed.
Nutrients 2021, 13(1), 109; https://doi.org/10.3390/nu13010109
Received: 10 November 2020
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Revised: 22 December 2020
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Accepted: 25 December 2020
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Published: 30 December 2020
(This article belongs to the Section Micronutrients and Human Health)
The relationship between depression and vitamin D deficiency is complex, with evidence mostly from studies affected by confounding and reverse causality. We examined the causality and direction of the relationship between 25-hydroxyvitamin D (25(OH)D) and depression in bi-directional Mendelian randomization (MR) analyses using information from up to 307,618 white British participants from the UK Biobank and summary results from the SUNLIGHT (n = 79,366) and Psychiatric Genomics consortia (PGC 113,154 cases and 218,523 controls). In observational analysis, the odds of depression decreased with higher 25(OH)D concentrations (adjusted odds ratio (OR) per 50% increase 0.95, 95%CI 0.94–0.96). In MR inverse variance weighted (IVW) using the UK Biobank, there was no association between genetically determined serum 25(OH)D and depression (OR per 50% higher 0.97, 95%CI 0.90–1.05) with consistent null association across all MR approaches and in data from PGC consortium. In contrast, genetic liability to depression was associated with lower 25(OH)D concentrations (MR IVW −3.26%, −4.94%–−1.55%), with the estimates remaining generally consistent after meta-analysing with the consortia. In conclusion, we found genetic evidence for a causal effect of depression on lower 25(OH)D concentrations, however we could not confirm a beneficial effect of nutritional vitamin D status on depression risk.
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Keywords:
25(OH)D; nutritional vitamin D status; depression; observational analysis; Mendelian randomization; UK Biobank
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MDPI and ACS Style
Mulugeta, A.; Lumsden, A.; Hyppönen, E. Relationship between Serum 25(OH)D and Depression: Causal Evidence from a Bi-Directional Mendelian Randomization Study. Nutrients 2021, 13, 109. https://doi.org/10.3390/nu13010109
AMA Style
Mulugeta A, Lumsden A, Hyppönen E. Relationship between Serum 25(OH)D and Depression: Causal Evidence from a Bi-Directional Mendelian Randomization Study. Nutrients. 2021; 13(1):109. https://doi.org/10.3390/nu13010109
Chicago/Turabian StyleMulugeta, Anwar, Amanda Lumsden, and Elina Hyppönen. 2021. "Relationship between Serum 25(OH)D and Depression: Causal Evidence from a Bi-Directional Mendelian Randomization Study" Nutrients 13, no. 1: 109. https://doi.org/10.3390/nu13010109
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