TY - JOUR
T1 - Micronutrients and Major Depression
T2 - A Mendelian Randomisation Study
AU - Carnegie, Rebecca E
AU - Zheng, Jie
AU - Borges, Maria C
AU - Jones, Hannah J
AU - Wade, Kaitlin H
AU - Sallis, Hannah M
AU - Martin, Richard M
AU - Lewis, Sarah J
AU - Evans, David M
AU - Revez, Joana A
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
AU - Evans, Jonathan
AU - Martin, Richard M
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/10/29
Y1 - 2024/10/29
N2 - 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 randomisation (MR), a method using genetic data to estimate causal effects given certain assumptions. 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.
AB - 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 randomisation (MR), a method using genetic data to estimate causal effects given certain assumptions. 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.
U2 - 10.3390/nu16213690
DO - 10.3390/nu16213690
M3 - Review article (Academic Journal)
C2 - 39519523
SN - 2072-6643
VL - 16
JO - Nutrients
JF - Nutrients
IS - 21
M1 - 3690
ER -