Calcium Homeostasis and Psychiatric Disorders: A Mendelian Randomization Study

Area of Science:

• Nutritional Psychiatry
• Metabolic Psychiatry
• Genetic Epidemiology

Background:

• Observational studies suggest links between calcium homeostasis and psychiatric disorders.
• Causality of these associations remains unconfirmed.
• Key calcium homeostasis hormones include calcium, 25-hydroxyvitamin D (25OHD), parathyroid hormone, and FGF23.

Purpose of the Study:

• To investigate the causal relationship between calcium homeostasis hormones and nine psychiatric disorders using Mendelian randomization.
• To evaluate the impact of psychiatric disorders on calcium homeostasis.
• To assess the role of 25OHD levels in schizophrenia.

Main Methods:

• Bidirectional Mendelian randomization (MR) analysis.
• Inverse variance weighted (IVW) method and MR Steiger test for causality.
• Sensitivity analyses including Cochran's Q test, MR-Egger intercept, funnel plot, and leave-one-out analysis.
• Multivariable MR (MVMR) to adjust for confounders like BMI and supplement intake.

Main Results:

• A significant causal association was found between schizophrenia (SCZ) and decreased serum 25OHD levels (P=2.39 × 10⁻⁷).
• This association persisted in MVMR analysis, even after adjusting for confounders.
• Autism spectrum disorder and bipolar disorder showed nominal associations with lower 25OHD.

Conclusions:

• Evidence supports a causal effect of psychiatric disorders on calcium homeostasis.
• Reduced 25OHD levels are a potential causal factor in schizophrenia.
• Clinical monitoring of 25OHD levels is advisable for psychiatric patients.