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ORIGINAL RESEARCH article

Front. Nutr.
Sec. Nutrigenomics
Volume 11 - 2024 | doi: 10.3389/fnut.2024.1415132
This article is part of the Research Topic Vitamin D: From Pathophysiology to Clinical Impact Volume II View all 22 articles

Association between 25(OH) Vitamin D and Schizophrenia: Shared genetic Correlation, Pleiotropy and Causality

Provisionally accepted
Guowei Rong Guowei Rong 1Xiaomin Li Xiaomin Li 1Huimin Lu Huimin Lu 2Mingzhu Su Mingzhu Su 1Yi Jin Yi Jin 1*
  • 1 Changzhou Wujin People's Hospital, Changning, Jiangsu Province, China
  • 2 The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China

The final, formatted version of the article will be published soon.

    Background: This study delves into the complex interplay between genetics, 25-hydroxyvitamin D (25OHD), and schizophrenia (SCZ). It leverages extensive sample data derived from Genome-Wide Association Studies (GWAS) to uncover genetic correlations.Methods: Employing Linkage Disequilibrium Score Regression (LDSC) and S-LDSC, this study investigates genetic connections between 25OHD and SCZ. It examines Single Nucleotide Polymorphism (SNP) heritability in specific tissues and incorporates diverse immune cell datasets for genetic enrichment analysis. Local genetic correlations were analyzed using HESS software, and pleiotropy analysis identified shared genetic loci in brain tissues. Hyprcoloc analysis was used to explore shared genetic factors between 25OHD, immune cells, and SCZ, complemented by a bidirectional Mendelian Randomization (MR) to probe potential causal links.We identified a significant negative genetic correlation between 25OHD levels and SCZ. PLACO analysis revealed 35 pleiotropic loci with strong enrichment in brain regions, particularly the cerebellum, frontal cortex, and hippocampus. Eight loci (1p34.2, 2p23.3, 3p21.1, 5q31.2, 12q23.2, 14q32.33, 16p13.3, and 16q24.3) exhibited strong colocalization, highlighting potential drug targets. Gene and tissue enrichment analyses emphasized neurological and immune-related mechanisms, including hyaluronan metabolism. Bidirectional MR analysis supported a causal effect of SCZ on 25OHD levels.Our study identifies NEK4 as a potential therapeutic target and highlights the involvement of hyaluronan metabolism in the genetic association between 25OHD and SCZ. These findings provide valuable insights into shared genetic pathways, immune-related connections, and causal interactions in the context of SCZ.

    Keywords: Vitamin D, Schizophrenia, genetic overlap, Mendelian randomization, Genome-Wide Association Study

    Received: 10 Apr 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Rong, Li, Lu, Su and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yi Jin, Changzhou Wujin People's Hospital, Changning, Jiangsu Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.