Version 1
: Received: 30 August 2024 / Approved: 30 August 2024 / Online: 2 September 2024 (11:18:21 CEST)
How to cite:
Carnegie, R. E.; Zheng, J.; Borges, M. C.; Jones, H. J.; Wade, K. H.; Sallis, H. M.; Lewis, S. J.; Evans, D. M.; Revez, J. A.; Evans, J.; Martin, R. M. Micronutrients and Major Depression: A Mendelian Randomization Study. Preprints2024, 2024082256. https://doi.org/10.20944/preprints202408.2256.v1
Carnegie, R. E.; Zheng, J.; Borges, M. C.; Jones, H. J.; Wade, K. H.; Sallis, H. M.; Lewis, S. J.; Evans, D. M.; Revez, J. A.; Evans, J.; Martin, R. M. Micronutrients and Major Depression: A Mendelian Randomization Study. Preprints 2024, 2024082256. https://doi.org/10.20944/preprints202408.2256.v1
Carnegie, R. E.; Zheng, J.; Borges, M. C.; Jones, H. J.; Wade, K. H.; Sallis, H. M.; Lewis, S. J.; Evans, D. M.; Revez, J. A.; Evans, J.; Martin, R. M. Micronutrients and Major Depression: A Mendelian Randomization Study. Preprints2024, 2024082256. https://doi.org/10.20944/preprints202408.2256.v1
APA Style
Carnegie, R. E., Zheng, J., Borges, M. C., Jones, H. J., Wade, K. H., Sallis, H. M., Lewis, S. J., Evans, D. M., Revez, J. A., Evans, J., & Martin, R. M. (2024). Micronutrients and Major Depression: A Mendelian Randomization Study. Preprints. https://doi.org/10.20944/preprints202408.2256.v1
Chicago/Turabian Style
Carnegie, R. E., Jonathan Evans and Richard M Martin. 2024 "Micronutrients and Major Depression: A Mendelian Randomization Study" Preprints. https://doi.org/10.20944/preprints202408.2256.v1
Abstract
Background: Various vitamins and minerals have been implicated in the aetiology of depression. Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomization (MR). Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566), and rMDD (cases=17,451; controls=62,482). Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g. cIVW), highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (ORcIVW 0.90 per SD increase; 95% CI 0.85- 0.95; p=0.0003); erythrocyte copper (ORcIVW 0.97; 95% CI 0.95- 0.99; p=0.0004); and 25(OH) vitamin D (ORcIVW 0.81; 0.66- 0.99; p=0.04). Apparent adverse effects of increased selenium on the risk of MDD (ORcIVW 1.03; 95% CI 1.02-1.05; p=0.0003) and rMDD (ORcIVW 1.08; 95% CI 1.00-1.08; p=0.06), and serum magnesium on rMDD (ORcIVW 1.21; 1.01- 1.44; p=0.04); were less consistent between methods and may be driven by pleiotropy. Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates, and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.
Keywords
mendelian randomization; vitamins; minerals; micronutrients; major depressive disorder
Subject
Medicine and Pharmacology, Psychiatry and Mental Health
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
