Epigenome-wide association study of Chinese monozygotic twins identifies DNA methylation loci associated with estimated glomerular filtration rate
Abstract Background DNA methylation (DNAm) has been shown in multiple studies to be associated with the estimated glomerular filtration rate (eGFR). However, studies focusing on Chinese populations are lacking. We conducted an epigenome-wide association study to investigate the association between D...
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BMC
2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06067-4 |
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| author | Xueting Qi Jingjing Wang Tong Wang Weijing Wang Dongfeng Zhang |
| author_facet | Xueting Qi Jingjing Wang Tong Wang Weijing Wang Dongfeng Zhang |
| author_sort | Xueting Qi |
| collection | DOAJ |
| description | Abstract Background DNA methylation (DNAm) has been shown in multiple studies to be associated with the estimated glomerular filtration rate (eGFR). However, studies focusing on Chinese populations are lacking. We conducted an epigenome-wide association study to investigate the association between DNAm and eGFR in Chinese monozygotic twins. Methods Genome-wide DNAm level was detected using Reduced Representation Bisulfite Sequencing test. Generalized estimation equation (GEE) was used to examine the association between Cytosine-phosphate-Guanines (CpGs) DNAm and eGFR. Inference about Causation from Examination of FAmiliaL CONfounding was employed to infer the causal relationship. The comb-p was used to identify differentially methylated regions (DMRs). GeneMANIA was used to analyze the gene interaction network. The Genomic Regions Enrichment of Annotations Tool enriched biological functions and pathways. Gene expression profiling sequencing was employed to measure mRNA expression levels, and the GEE model was used to investigate the association between gene expression and eGFR. The candidate gene was validated in a community population by calculating the methylation risk score (MRS). Results A total of 80 CpGs and 28 DMRs, located at genes such as OLIG2, SYNGR3, LONP1, CDCP1, and SHANK1, achieved genome-wide significance level (FDR < 0.05). The causal effect of DNAm on eGFR was supported by 12 CpGs located at genes such as SYNGR3 and C9orf3. In contrast, the causal effect of eGFR on DNAm is proved by 13 CpGs located at genes such as EPHB3 and MLLT1. Enrichment analysis revealed several important biological functions and pathways related to eGFR, including alpha-2A adrenergic receptor binding pathway and corticotropin-releasing hormone receptor activity pathway. GeneMANIA results showed that SYNGR3 was co-expressed with MLLT1 and had genetic interactions with AFF4 and EDIL3. Gene expression analysis found that SYNGR3 expression was negatively associated with eGFR. Validation analysis showed that the MRS of SYNGR3 was positively associated with low eGFR levels. Conclusions We identified a set of CpGs, DMRs, and pathways potentially associated with eGFR, particularly in the SYNGR3 gene. These findings provided new insights into the epigenetic modifications related to the decline in eGFR and chronic kidney disease. |
| format | Article |
| id | doaj-art-1489750f54294467b2a3a9d28d0db348 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-1489750f54294467b2a3a9d28d0db3482025-01-26T12:50:20ZengBMCJournal of Translational Medicine1479-58762025-01-0123111310.1186/s12967-025-06067-4Epigenome-wide association study of Chinese monozygotic twins identifies DNA methylation loci associated with estimated glomerular filtration rateXueting Qi0Jingjing Wang1Tong Wang2Weijing Wang3Dongfeng Zhang4Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityDepartment of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityDepartment of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityDepartment of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityDepartment of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityAbstract Background DNA methylation (DNAm) has been shown in multiple studies to be associated with the estimated glomerular filtration rate (eGFR). However, studies focusing on Chinese populations are lacking. We conducted an epigenome-wide association study to investigate the association between DNAm and eGFR in Chinese monozygotic twins. Methods Genome-wide DNAm level was detected using Reduced Representation Bisulfite Sequencing test. Generalized estimation equation (GEE) was used to examine the association between Cytosine-phosphate-Guanines (CpGs) DNAm and eGFR. Inference about Causation from Examination of FAmiliaL CONfounding was employed to infer the causal relationship. The comb-p was used to identify differentially methylated regions (DMRs). GeneMANIA was used to analyze the gene interaction network. The Genomic Regions Enrichment of Annotations Tool enriched biological functions and pathways. Gene expression profiling sequencing was employed to measure mRNA expression levels, and the GEE model was used to investigate the association between gene expression and eGFR. The candidate gene was validated in a community population by calculating the methylation risk score (MRS). Results A total of 80 CpGs and 28 DMRs, located at genes such as OLIG2, SYNGR3, LONP1, CDCP1, and SHANK1, achieved genome-wide significance level (FDR < 0.05). The causal effect of DNAm on eGFR was supported by 12 CpGs located at genes such as SYNGR3 and C9orf3. In contrast, the causal effect of eGFR on DNAm is proved by 13 CpGs located at genes such as EPHB3 and MLLT1. Enrichment analysis revealed several important biological functions and pathways related to eGFR, including alpha-2A adrenergic receptor binding pathway and corticotropin-releasing hormone receptor activity pathway. GeneMANIA results showed that SYNGR3 was co-expressed with MLLT1 and had genetic interactions with AFF4 and EDIL3. Gene expression analysis found that SYNGR3 expression was negatively associated with eGFR. Validation analysis showed that the MRS of SYNGR3 was positively associated with low eGFR levels. Conclusions We identified a set of CpGs, DMRs, and pathways potentially associated with eGFR, particularly in the SYNGR3 gene. These findings provided new insights into the epigenetic modifications related to the decline in eGFR and chronic kidney disease.https://doi.org/10.1186/s12967-025-06067-4Estimated glomerular filtration rateDNA methylationCausalityMonozygotic twinsEpigenome-wide association study |
| spellingShingle | Xueting Qi Jingjing Wang Tong Wang Weijing Wang Dongfeng Zhang Epigenome-wide association study of Chinese monozygotic twins identifies DNA methylation loci associated with estimated glomerular filtration rate Journal of Translational Medicine Estimated glomerular filtration rate DNA methylation Causality Monozygotic twins Epigenome-wide association study |
| title | Epigenome-wide association study of Chinese monozygotic twins identifies DNA methylation loci associated with estimated glomerular filtration rate |
| title_full | Epigenome-wide association study of Chinese monozygotic twins identifies DNA methylation loci associated with estimated glomerular filtration rate |
| title_fullStr | Epigenome-wide association study of Chinese monozygotic twins identifies DNA methylation loci associated with estimated glomerular filtration rate |
| title_full_unstemmed | Epigenome-wide association study of Chinese monozygotic twins identifies DNA methylation loci associated with estimated glomerular filtration rate |
| title_short | Epigenome-wide association study of Chinese monozygotic twins identifies DNA methylation loci associated with estimated glomerular filtration rate |
| title_sort | epigenome wide association study of chinese monozygotic twins identifies dna methylation loci associated with estimated glomerular filtration rate |
| topic | Estimated glomerular filtration rate DNA methylation Causality Monozygotic twins Epigenome-wide association study |
| url | https://doi.org/10.1186/s12967-025-06067-4 |
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