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Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causality
Guo-Wei Rong1,2, Xiao-Min Li1,3,4, Hui-Min Lu5
1The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China.
Frontiers in Nutrition
|December 30, 2024
Summary
This study reveals a genetic link between vitamin D levels and schizophrenia (SCZ), finding that lower vitamin D is associated with increased SCZ risk. It also suggests schizophrenia may causally influence vitamin D levels.
Area of Science:
- Neurogenetics
- Psychiatric Genetics
- Nutritional Neuroscience
Background:
- Investigates the complex genetic relationship between 25-hydroxyvitamin D (25OHD) and schizophrenia (SCZ).
- Utilizes large-scale Genome-Wide Association Studies (GWAS) data to explore genetic correlations.
Purpose of the Study:
- To uncover genetic connections between 25OHD levels and SCZ.
- To identify shared genetic loci and potential causal relationships between 25OHD and SCZ.
- To explore the role of immune and neurological pathways in this association.
Main Methods:
- Employed Linkage Disequilibrium Score Regression (LDSC) and S-LDSC for genetic correlation analysis.
- Performed SNP heritability, genetic enrichment analysis using immune cell datasets, and local genetic correlation analysis (HESS).
- Utilized Hyprcoloc and bidirectional Mendelian Randomization (MR) to investigate shared genetic factors and causality.
Main Results:
- Identified a significant negative genetic correlation between 25OHD levels and SCZ.
- Discovered 35 pleiotropic loci enriched in brain regions, with eight showing strong colocalization.
- Bidirectional MR analysis indicated a causal effect of SCZ on 25OHD levels.
Conclusions:
- NEK4 identified as a potential therapeutic target.
- Hyaluronan metabolism implicated in the genetic association between 25OHD and SCZ.
- Findings offer insights into shared genetic pathways, immune links, and causal interactions in SCZ.
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