Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causality
BackgroundThis 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.MethodsEmploying Linkage Disequilibrium Score Regressi...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2024.1415132/full |
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| author | Guo-Wei Rong Guo-Wei Rong Xiao-Min Li Xiao-Min Li Xiao-Min Li Hui-Min Lu Ming-Zhu Su Ming-Zhu Su Yi Jin Yi Jin Yi Jin |
| author_facet | Guo-Wei Rong Guo-Wei Rong Xiao-Min Li Xiao-Min Li Xiao-Min Li Hui-Min Lu Ming-Zhu Su Ming-Zhu Su Yi Jin Yi Jin Yi Jin |
| author_sort | Guo-Wei Rong |
| collection | DOAJ |
| description | BackgroundThis 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.MethodsEmploying 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.ResultsWe 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.ConclusionOur 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. |
| format | Article |
| id | doaj-art-a90e011c670846f0a7956117dbcbf7ce |
| institution | OA Journals |
| issn | 2296-861X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Nutrition |
| spelling | doaj-art-a90e011c670846f0a7956117dbcbf7ce2025-08-20T01:58:54ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2024-12-011110.3389/fnut.2024.14151321415132Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causalityGuo-Wei Rong0Guo-Wei Rong1Xiao-Min Li2Xiao-Min Li3Xiao-Min Li4Hui-Min Lu5Ming-Zhu Su6Ming-Zhu Su7Yi Jin8Yi Jin9Yi Jin10The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, ChinaDepartment of Orthopedics, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, ChinaThe Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, ChinaJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Pharmacy, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, ChinaDepartment of Outpatient and Emergency, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaThe Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, ChinaDepartment of Good Clinical Practice, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, ChinaThe Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, ChinaJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Pharmacy, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, ChinaBackgroundThis 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.MethodsEmploying 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.ResultsWe 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fnut.2024.1415132/fullvitamin Dschizophreniagenetic overlapMendelian randomizationgenome-wide association study |
| spellingShingle | Guo-Wei Rong Guo-Wei Rong Xiao-Min Li Xiao-Min Li Xiao-Min Li Hui-Min Lu Ming-Zhu Su Ming-Zhu Su Yi Jin Yi Jin Yi Jin Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causality Frontiers in Nutrition vitamin D schizophrenia genetic overlap Mendelian randomization genome-wide association study |
| title | Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causality |
| title_full | Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causality |
| title_fullStr | Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causality |
| title_full_unstemmed | Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causality |
| title_short | Association between 25(OH) vitamin D and schizophrenia: shared genetic correlation, pleiotropy, and causality |
| title_sort | association between 25 oh vitamin d and schizophrenia shared genetic correlation pleiotropy and causality |
| topic | vitamin D schizophrenia genetic overlap Mendelian randomization genome-wide association study |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2024.1415132/full |
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