Genome‐Wide 5‐Methylcytosine and 5‐Hydroxymethylcytosine Signatures Analysis of Plasma Cell‐Free DNA in Schizophrenia
ABSTRACT Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder that affects ∼1% of people globally. Despite extensive research, there remains a lack of biomarkers for SCZ diagnosis and disease pathogenesis delineation. Cell‐free DNA (cfDNA), which carries the genetic and epigenetic sig...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-08-01
|
| Series: | MedComm |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mco2.70293 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849341764211572736 |
|---|---|
| author | Gang Xue Xia Wei Li Li Qi Zhang Shanming Liu Jun Zhang Wen Hu Qiannan Zhao Wenjing Zhang Chunyan Luo Qiyong Gong Bo Zhang Dan Xie Su Lui |
| author_facet | Gang Xue Xia Wei Li Li Qi Zhang Shanming Liu Jun Zhang Wen Hu Qiannan Zhao Wenjing Zhang Chunyan Luo Qiyong Gong Bo Zhang Dan Xie Su Lui |
| author_sort | Gang Xue |
| collection | DOAJ |
| description | ABSTRACT Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder that affects ∼1% of people globally. Despite extensive research, there remains a lack of biomarkers for SCZ diagnosis and disease pathogenesis delineation. Cell‐free DNA (cfDNA), which carries the genetic and epigenetic signatures of origin tissue cells, may provide a noninvasive method for biomarker discovery. We performed cfDNA 5‐methylcytosine (5mC) and 5‐hydroxymethylcytosine (5hmC) sequencing of plasma samples from 66 individuals with SCZ and 77 healthy controls. We identified 954 differentially 5mC methylated regions (DMRs) and 1474 differentially 5hmC hydroxymethylated regions (DhMRs) that showed distinct patterns between SCZ and control samples. Many DMRs and DhMRs were associated with genes specifically expressed in brain tissues and were enriched in neuronal functions, as well as were enriched for genome‐wide association study (GWAS) of psychiatric and brain volume traits. Additionally, colocalization analysis revealed that DhMRs but not DMRs locations significantly overlapped with GWAS‐identified genomic loci of SCZ. Moreover, we observed associations between DMRs and DhMRs with brain regional measurements depicted by magnetic resonance imaging. Together, our findings indicated that cfDNA 5mC and 5hmC patterns are accessible epigenomic signatures that can serve as potential biomarkers and to help delineate SCZ pathogenesis. |
| format | Article |
| id | doaj-art-4271c19e6aa8467398429e4eb257ccd3 |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-4271c19e6aa8467398429e4eb257ccd32025-08-20T03:43:34ZengWileyMedComm2688-26632025-08-0168n/an/a10.1002/mco2.70293Genome‐Wide 5‐Methylcytosine and 5‐Hydroxymethylcytosine Signatures Analysis of Plasma Cell‐Free DNA in SchizophreniaGang Xue0Xia Wei1Li Li2Qi Zhang3Shanming Liu4Jun Zhang5Wen Hu6Qiannan Zhao7Wenjing Zhang8Chunyan Luo9Qiyong Gong10Bo Zhang11Dan Xie12Su Lui13Laboratory of Omics Technology and Bioinformatics Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu Sichuan ChinaDepartment of Radiology and Functional and Molecular Imaging Key Laboratory of Sichuan Province West China Hospital of Sichuan University Chengdu ChinaDepartment of Nuclear Medicine West China Hospital Sichuan University Chengdu ChinaDepartment of Radiology and Functional and Molecular Imaging Key Laboratory of Sichuan Province West China Hospital of Sichuan University Chengdu ChinaMental Health Center West China Hospital Sichuan University Chengdu ChinaTailai Inc. Chengdu Sichuan ChinaTailai Inc. Chengdu Sichuan ChinaDepartment of Radiology and Functional and Molecular Imaging Key Laboratory of Sichuan Province West China Hospital of Sichuan University Chengdu ChinaDepartment of Radiology and Functional and Molecular Imaging Key Laboratory of Sichuan Province West China Hospital of Sichuan University Chengdu ChinaDepartment of Radiology and Functional and Molecular Imaging Key Laboratory of Sichuan Province West China Hospital of Sichuan University Chengdu ChinaDepartment of Radiology and Functional and Molecular Imaging Key Laboratory of Sichuan Province West China Hospital of Sichuan University Chengdu ChinaMental Health Center West China Hospital Sichuan University Chengdu ChinaLaboratory of Omics Technology and Bioinformatics Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu Sichuan ChinaDepartment of Radiology and Functional and Molecular Imaging Key Laboratory of Sichuan Province West China Hospital of Sichuan University Chengdu ChinaABSTRACT Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder that affects ∼1% of people globally. Despite extensive research, there remains a lack of biomarkers for SCZ diagnosis and disease pathogenesis delineation. Cell‐free DNA (cfDNA), which carries the genetic and epigenetic signatures of origin tissue cells, may provide a noninvasive method for biomarker discovery. We performed cfDNA 5‐methylcytosine (5mC) and 5‐hydroxymethylcytosine (5hmC) sequencing of plasma samples from 66 individuals with SCZ and 77 healthy controls. We identified 954 differentially 5mC methylated regions (DMRs) and 1474 differentially 5hmC hydroxymethylated regions (DhMRs) that showed distinct patterns between SCZ and control samples. Many DMRs and DhMRs were associated with genes specifically expressed in brain tissues and were enriched in neuronal functions, as well as were enriched for genome‐wide association study (GWAS) of psychiatric and brain volume traits. Additionally, colocalization analysis revealed that DhMRs but not DMRs locations significantly overlapped with GWAS‐identified genomic loci of SCZ. Moreover, we observed associations between DMRs and DhMRs with brain regional measurements depicted by magnetic resonance imaging. Together, our findings indicated that cfDNA 5mC and 5hmC patterns are accessible epigenomic signatures that can serve as potential biomarkers and to help delineate SCZ pathogenesis.https://doi.org/10.1002/mco2.70293schizophreniacell‐free DNA5‐methylcytosine5‐hydroxymethylcytosinemagnetic resonance imaging |
| spellingShingle | Gang Xue Xia Wei Li Li Qi Zhang Shanming Liu Jun Zhang Wen Hu Qiannan Zhao Wenjing Zhang Chunyan Luo Qiyong Gong Bo Zhang Dan Xie Su Lui Genome‐Wide 5‐Methylcytosine and 5‐Hydroxymethylcytosine Signatures Analysis of Plasma Cell‐Free DNA in Schizophrenia MedComm schizophrenia cell‐free DNA 5‐methylcytosine 5‐hydroxymethylcytosine magnetic resonance imaging |
| title | Genome‐Wide 5‐Methylcytosine and 5‐Hydroxymethylcytosine Signatures Analysis of Plasma Cell‐Free DNA in Schizophrenia |
| title_full | Genome‐Wide 5‐Methylcytosine and 5‐Hydroxymethylcytosine Signatures Analysis of Plasma Cell‐Free DNA in Schizophrenia |
| title_fullStr | Genome‐Wide 5‐Methylcytosine and 5‐Hydroxymethylcytosine Signatures Analysis of Plasma Cell‐Free DNA in Schizophrenia |
| title_full_unstemmed | Genome‐Wide 5‐Methylcytosine and 5‐Hydroxymethylcytosine Signatures Analysis of Plasma Cell‐Free DNA in Schizophrenia |
| title_short | Genome‐Wide 5‐Methylcytosine and 5‐Hydroxymethylcytosine Signatures Analysis of Plasma Cell‐Free DNA in Schizophrenia |
| title_sort | genome wide 5 methylcytosine and 5 hydroxymethylcytosine signatures analysis of plasma cell free dna in schizophrenia |
| topic | schizophrenia cell‐free DNA 5‐methylcytosine 5‐hydroxymethylcytosine magnetic resonance imaging |
| url | https://doi.org/10.1002/mco2.70293 |
| work_keys_str_mv | AT gangxue genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT xiawei genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT lili genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT qizhang genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT shanmingliu genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT junzhang genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT wenhu genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT qiannanzhao genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT wenjingzhang genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT chunyanluo genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT qiyonggong genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT bozhang genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT danxie genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia AT sului genomewide5methylcytosineand5hydroxymethylcytosinesignaturesanalysisofplasmacellfreednainschizophrenia |