Longitudinal association of peripheral blood DNA methylation with liver fat content: distinguishing between predictors and biomarkers
Abstract Background Alterations in DNA methylation (DNAm) have been observed in patients with fatty liver, but whether they are cause or consequence remains unknown. The study aimed to investigate longitudinal association of epigenome-wide DNAm with liver fat content (LFC) in Chinese participants, a...
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BMC
2024-09-01
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| Series: | Lipids in Health and Disease |
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| Online Access: | https://doi.org/10.1186/s12944-024-02304-9 |
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| author | Hailuan Zeng Wenran Li Mingfeng Xia Jieyu Ge Hui Ma Lingyan Chen Baishen Pan Huandong Lin Sijia Wang Xin Gao |
| author_facet | Hailuan Zeng Wenran Li Mingfeng Xia Jieyu Ge Hui Ma Lingyan Chen Baishen Pan Huandong Lin Sijia Wang Xin Gao |
| author_sort | Hailuan Zeng |
| collection | DOAJ |
| description | Abstract Background Alterations in DNA methylation (DNAm) have been observed in patients with fatty liver, but whether they are cause or consequence remains unknown. The study aimed to investigate longitudinal association of epigenome-wide DNAm with liver fat content (LFC) in Chinese participants, and explore their temporal relationships. Methods Data were obtained from 2 waves over a four-year time period of the Shanghai Changfeng Study (discovery, n = 407 and replication, n = 126). LFC and peripheral blood DNAm were repeatedly measured using quantitative hepatic ultrasonography and the 850 K Illumina EPIC BeadChip, respectively. Longitudinal and cross-sectional epigenome-wide association studies (EWASs) were conducted with linear mixed model and linear regression model, respectively. Meta-analysis was performed using METAL. Cross-lagged panel analysis (CLPA) was carried out to infer temporal relationships between the significant CpGs and LFC. Results Longitudinal EWAS identified cg11024682 (SREBF1), cg06500161 (ABCG1), cg16740586 (ABCG1), cg15659943 (ABCA1) and cg00163198 (SNX19) significantly associated with LFC with P < 1e-7. Another 6 of the 22 previously reported CpGs were replicated in the present longitudinal EWAS. CLPA showed longitudinal effects of cg11024682 (SREBF1) (β = 0.14 [0.06, 0.23]), cg16740586 (ABCG1) (β = 0.17 [0.08, 0.25]), cg06500161 (ABCG1) (β = 0.12 [0.03, 0.20]), cg17901584 (DHCR24) (β = -0.10 [-0.18, -0.02]), cg00574958 (CPT1A) (β = -0.09 [-0.17, -0.01]), cg08309687 (LINC00649) (β = -0.11 [-0.19, -0.03]), and cg27243685 (ABCG1) (β = 0.09 [0.01, 0.18]) on subsequent LFC. The effects were attenuated when further adjusting for body mass index. High levels of LFC led to alterations in DNAm of cg15659943 (ABCA1) (β = 0.13 [0.04, 0.21]), cg07162647 (β = -0.11 [-0.19, -0.03]), cg06500161 (ABCG1) (β = 0.10 [0.02, 0.18]), and cg27243685 (ABCG1) (β = 0.10 [0.02, 0.18]). Conclusions Blood DNAm at SREBF1, ABCG1, DHCR24, CPT1A, and LINC00649 may be predictors of subsequent LFC change. The effects of DNAm at SREBF1 and ABCG1 on LFC were partially influenced by obesity. The findings have potential implications in understanding disease pathogenesis and highlight the potential of DNAm for early detection or intervention of fatty liver. |
| format | Article |
| id | doaj-art-246843172265432ea31c7e1abe31c36c |
| institution | Kabale University |
| issn | 1476-511X |
| language | English |
| publishDate | 2024-09-01 |
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| series | Lipids in Health and Disease |
| spelling | doaj-art-246843172265432ea31c7e1abe31c36c2024-12-22T12:44:52ZengBMCLipids in Health and Disease1476-511X2024-09-0123111310.1186/s12944-024-02304-9Longitudinal association of peripheral blood DNA methylation with liver fat content: distinguishing between predictors and biomarkersHailuan Zeng0Wenran Li1Mingfeng Xia2Jieyu Ge3Hui Ma4Lingyan Chen5Baishen Pan6Huandong Lin7Sijia Wang8Xin Gao9Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan UniversityCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of SciencesDepartment of Endocrinology and Metabolism, Zhongshan Hospital, Fudan UniversityCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of SciencesDepartment of Geriatrics, Zhongshan Hospital, Fudan UniversityDepartment of Geriatrics, Zhongshan Hospital, Fudan UniversityDepartment of Laboratory Medicine, Zhongshan Hospital, Fudan UniversityDepartment of Endocrinology and Metabolism, Zhongshan Hospital, Fudan UniversityCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of SciencesDepartment of Endocrinology and Metabolism, Zhongshan Hospital, Fudan UniversityAbstract Background Alterations in DNA methylation (DNAm) have been observed in patients with fatty liver, but whether they are cause or consequence remains unknown. The study aimed to investigate longitudinal association of epigenome-wide DNAm with liver fat content (LFC) in Chinese participants, and explore their temporal relationships. Methods Data were obtained from 2 waves over a four-year time period of the Shanghai Changfeng Study (discovery, n = 407 and replication, n = 126). LFC and peripheral blood DNAm were repeatedly measured using quantitative hepatic ultrasonography and the 850 K Illumina EPIC BeadChip, respectively. Longitudinal and cross-sectional epigenome-wide association studies (EWASs) were conducted with linear mixed model and linear regression model, respectively. Meta-analysis was performed using METAL. Cross-lagged panel analysis (CLPA) was carried out to infer temporal relationships between the significant CpGs and LFC. Results Longitudinal EWAS identified cg11024682 (SREBF1), cg06500161 (ABCG1), cg16740586 (ABCG1), cg15659943 (ABCA1) and cg00163198 (SNX19) significantly associated with LFC with P < 1e-7. Another 6 of the 22 previously reported CpGs were replicated in the present longitudinal EWAS. CLPA showed longitudinal effects of cg11024682 (SREBF1) (β = 0.14 [0.06, 0.23]), cg16740586 (ABCG1) (β = 0.17 [0.08, 0.25]), cg06500161 (ABCG1) (β = 0.12 [0.03, 0.20]), cg17901584 (DHCR24) (β = -0.10 [-0.18, -0.02]), cg00574958 (CPT1A) (β = -0.09 [-0.17, -0.01]), cg08309687 (LINC00649) (β = -0.11 [-0.19, -0.03]), and cg27243685 (ABCG1) (β = 0.09 [0.01, 0.18]) on subsequent LFC. The effects were attenuated when further adjusting for body mass index. High levels of LFC led to alterations in DNAm of cg15659943 (ABCA1) (β = 0.13 [0.04, 0.21]), cg07162647 (β = -0.11 [-0.19, -0.03]), cg06500161 (ABCG1) (β = 0.10 [0.02, 0.18]), and cg27243685 (ABCG1) (β = 0.10 [0.02, 0.18]). Conclusions Blood DNAm at SREBF1, ABCG1, DHCR24, CPT1A, and LINC00649 may be predictors of subsequent LFC change. The effects of DNAm at SREBF1 and ABCG1 on LFC were partially influenced by obesity. The findings have potential implications in understanding disease pathogenesis and highlight the potential of DNAm for early detection or intervention of fatty liver.https://doi.org/10.1186/s12944-024-02304-9Liver fat contentDNA methylationCross-lagged panel analysisLongitudinal study |
| spellingShingle | Hailuan Zeng Wenran Li Mingfeng Xia Jieyu Ge Hui Ma Lingyan Chen Baishen Pan Huandong Lin Sijia Wang Xin Gao Longitudinal association of peripheral blood DNA methylation with liver fat content: distinguishing between predictors and biomarkers Lipids in Health and Disease Liver fat content DNA methylation Cross-lagged panel analysis Longitudinal study |
| title | Longitudinal association of peripheral blood DNA methylation with liver fat content: distinguishing between predictors and biomarkers |
| title_full | Longitudinal association of peripheral blood DNA methylation with liver fat content: distinguishing between predictors and biomarkers |
| title_fullStr | Longitudinal association of peripheral blood DNA methylation with liver fat content: distinguishing between predictors and biomarkers |
| title_full_unstemmed | Longitudinal association of peripheral blood DNA methylation with liver fat content: distinguishing between predictors and biomarkers |
| title_short | Longitudinal association of peripheral blood DNA methylation with liver fat content: distinguishing between predictors and biomarkers |
| title_sort | longitudinal association of peripheral blood dna methylation with liver fat content distinguishing between predictors and biomarkers |
| topic | Liver fat content DNA methylation Cross-lagged panel analysis Longitudinal study |
| url | https://doi.org/10.1186/s12944-024-02304-9 |
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