Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins
Background: The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins.Methods: DN...
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1378680/full |
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| author | Jia Luo Weijing Wang Jingxian Li Haiping Duan Haiping Duan Chunsheng Xu Chunsheng Xu Xiaocao Tian Xiaocao Tian Dongfeng Zhang |
| author_facet | Jia Luo Weijing Wang Jingxian Li Haiping Duan Haiping Duan Chunsheng Xu Chunsheng Xu Xiaocao Tian Xiaocao Tian Dongfeng Zhang |
| author_sort | Jia Luo |
| collection | DOAJ |
| description | Background: The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins.Methods: DNA methylation (DNAm) profiling was conducted in whole blood samples through Reduced Representation Bisulfite Sequencing method. Generalized estimating equation was applied to regress the DNAm of each CpG with HGS. The Genomic Regions Enrichment of Annotations Tool was used to perform enrichment analysis. Differentially methylated regions (DMRs) were detected using comb-p. Causal inference was performed using Inference about Causation through Examination of Familial Confounding method. Finally, we validated candidate CpGs in community residents.Results: We identified 25 CpGs reaching genome-wide significance level. These CpGs located in 9 genes, especially FBLN1, RXRA, and ABHD14B. Many enriched terms highlighted calcium channels, neuromuscular junctions, and skeletal muscle organ development. We identified 21 DMRs of HGS, with several DMRs within FBLN1, SLC30A8, CST3, and SOCS3. Causal inference indicated that the DNAm of 16 top CpGs within FBLN1, RXRA, ABHD14B, MFSD6, and TYW1B might influence HGS, while HGS influenced DNAm at two CpGs within FBLN1 and RXRA. In validation analysis, methylation levels of six CpGs mapped to FLBN1 and one CpG mapped to ABHD14B were negatively associated with HGS weakness in community population.Conclusion: Our study identified multiple DNAm variants potentially related to HGS, especially CpGs within FBLN1 and ABHD14B. These findings provide new clues to the epigenetic modification underlying muscle strength decline. |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-24T14:26:19Z |
| publishDate | 2024-04-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-fe2cab880bf44f999f686cf682f0b7092024-04-03T05:05:04ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-04-011210.3389/fcell.2024.13786801378680Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twinsJia Luo0Weijing Wang1Jingxian Li2Haiping Duan3Haiping Duan4Chunsheng Xu5Chunsheng Xu6Xiaocao Tian7Xiaocao Tian8Dongfeng Zhang9Department of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao, Shandong, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao, Shandong, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao, Shandong, ChinaQingdao Municipal Centre for Disease Control and Prevention, Qingdao, Shandong, ChinaQingdao Institute of Preventive Medicine, Qingdao, Shandong, ChinaQingdao Municipal Centre for Disease Control and Prevention, Qingdao, Shandong, ChinaQingdao Institute of Preventive Medicine, Qingdao, Shandong, ChinaQingdao Municipal Centre for Disease Control and Prevention, Qingdao, Shandong, ChinaQingdao Institute of Preventive Medicine, Qingdao, Shandong, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao, Shandong, ChinaBackground: The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins.Methods: DNA methylation (DNAm) profiling was conducted in whole blood samples through Reduced Representation Bisulfite Sequencing method. Generalized estimating equation was applied to regress the DNAm of each CpG with HGS. The Genomic Regions Enrichment of Annotations Tool was used to perform enrichment analysis. Differentially methylated regions (DMRs) were detected using comb-p. Causal inference was performed using Inference about Causation through Examination of Familial Confounding method. Finally, we validated candidate CpGs in community residents.Results: We identified 25 CpGs reaching genome-wide significance level. These CpGs located in 9 genes, especially FBLN1, RXRA, and ABHD14B. Many enriched terms highlighted calcium channels, neuromuscular junctions, and skeletal muscle organ development. We identified 21 DMRs of HGS, with several DMRs within FBLN1, SLC30A8, CST3, and SOCS3. Causal inference indicated that the DNAm of 16 top CpGs within FBLN1, RXRA, ABHD14B, MFSD6, and TYW1B might influence HGS, while HGS influenced DNAm at two CpGs within FBLN1 and RXRA. In validation analysis, methylation levels of six CpGs mapped to FLBN1 and one CpG mapped to ABHD14B were negatively associated with HGS weakness in community population.Conclusion: Our study identified multiple DNAm variants potentially related to HGS, especially CpGs within FBLN1 and ABHD14B. These findings provide new clues to the epigenetic modification underlying muscle strength decline.https://www.frontiersin.org/articles/10.3389/fcell.2024.1378680/fullepigeneticsDNA methylationmonozygotic twinshandgrip strengthcausal inference |
| spellingShingle | Jia Luo Weijing Wang Jingxian Li Haiping Duan Haiping Duan Chunsheng Xu Chunsheng Xu Xiaocao Tian Xiaocao Tian Dongfeng Zhang Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins Frontiers in Cell and Developmental Biology epigenetics DNA methylation monozygotic twins handgrip strength causal inference |
| title | Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins |
| title_full | Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins |
| title_fullStr | Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins |
| title_full_unstemmed | Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins |
| title_short | Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins |
| title_sort | epigenome wide association study identifies dna methylation loci associated with handgrip strength in chinese monozygotic twins |
| topic | epigenetics DNA methylation monozygotic twins handgrip strength causal inference |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1378680/full |
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