Abstract
While observational studies show an association between 25(OH)vitamin D concentrations and depressive symptoms, intervention studies, which examine the preventive effects of vitamin D supplementation on the development of depression, are lacking. To estimate the role of lowered 25(OH)vitamin D concentrations in the etiology of depressive disorders, we conducted a two-sample Mendelian randomization (MR) study on depression, i.e., “depressive symptoms” (DS, n = 161,460) and “broad depression” (BD, n = 113,769 cases and 208,811 controls). Six single nucleotide polymorphisms (SNPs), which were genome-wide significantly associated with 25(OH)vitamin D concentrations in 79,366 subjects from the SUNLIGHT genome-wide association study (GWAS), were used as an instrumental variable. None of the six SNPs was associated with DS or BD (all p > 0.05). MR analysis revealed no causal effects of 25(OH)vitamin D concentration, either on DS (inverse variance weighted (IVW); b = 0.025, SE = 0.038, p = 0.52) or on BD (IVW; b = 0.020, SE = 0.012, p = 0.10). Sensitivity analyses confirmed that 25(OH)vitamin D concentrations were not significantly associated with DS or BD. The findings from this MR study indicate no causal relationship between vitamin D concentrations and depressive symptoms, or broad depression. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.
Highlights
Depressive disorders are the most common mental disorders worldwide, with more than 300 million people having been affected, in 2015 [1]
The following studies were included in the SUNLIGHT genome-wide association study (GWAS): 1958 British Birth (1956BC), the Cardiovascular Health Study (CHS), the Framingham Heart Study (FHS), Gothenburg Osteoporosis and Obesity Determinants (GOOD), the Health, Aging, and Body Composition study (Health ABC), the Study of Indiana Women (Indiana), the Northern Finland Birth Cohort 1966 (NFBC), the Old Older Amish Study (OOA), the Rotterdam
For our Mendelian randomization (MR) study we used independent single nucleotide polymorphisms (SNPs) of all six loci as genetic instruments, which were genome-wide significantly associated with the exposure of interest [18]
Summary
Depressive disorders are the most common mental disorders worldwide, with more than 300 million people having been affected, in 2015 [1]. Considering the increasing evidence for an inverse association between diet quality and mental. A number of studies have confirmed a relationship between vitamin D levels and mental health already in childhood and adolescence. The majority of such studies focused on the autism spectrum disorders and ADHD [4]. The few observational studies on depression in adolescence seemed to confirm the suggested inverse association between 25(OH)vitamin D concentrations (recommended biomarker for vitamin D status), and depression or emotional problems [5,6,7]. Findings from observational studies are not sufficient to draw conclusions on cause–effect relationships
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