Zhiyu Wu1, Lu Chen1, Xuanming Hong1, Jiahui Si2, Weihua Cao1, Canqing Yu1,3, Tao Huang1, Dianjianyi Sun1, Chunxiao Liao1, Yuanjie Pang1, Zengchang Pang4, Liming Cong5, Hua Wang6, Xianping Wu7, Yu Liu8, Yu Guo9, Zhengming Chen10, Jun Lv1,3,11, Wenjing Gao12, Liming Li13,14. 1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, China. 2. National Institute of Health Data Science at Peking University, Peking University, Beijing, 100191, China. 3. Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, 100191, China. 4. Qingdao Center for Disease Control and Prevention, Qingdao, 266033, China. 5. Zhejiang Center for Disease Control and Prevention, Hangzhou, 310051, China. 6. Jiangsu Center for Disease Control and Prevention, Nanjing, 210008, China. 7. Sichuan Center for Disease Control and Prevention, Chengdu, 610041, China. 8. Heilongjiang Center for Disease Control and Prevention, Harbin, 150090, China. 9. Fuwai hospital Chinese Academy of Medical Sciences, Beijing, 100037, China. 10. Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. 11. Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, 100191, China. 12. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, China. pkuepigwj@126.com. 13. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, China. lmlee@vip.163.com. 14. Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, 100191, China. lmlee@vip.163.com.
Abstract
BACKGROUND: The associations between blood lipids and DNA methylation have been investigated in epigenome-wide association studies mainly among European ancestry populations. Several studies have explored the direction of the association using cross-sectional data, while evidence of longitudinal data is still lacking. RESULTS: We tested the associations between peripheral blood leukocytes DNA methylation and four lipid measures from Illumina 450 K or EPIC arrays in 1084 participants from the Chinese National Twin Registry and replicated the result in 988 participants from the China Kadoorie Biobank. A total of 23 associations of 19 CpG sites were identified, with 4 CpG sites located in or adjacent to 3 genes (TMEM49, SNX5/SNORD17 and CCDC7) being novel. Among the validated associations, we conducted a cross-lagged analysis to explore the temporal sequence and found temporal associations of methylation levels of 2 CpG sites with triglyceride and 2 CpG sites with high-density lipoprotein-cholesterol (HDL-C) in all twins. In addition, methylation levels of cg11024682 located in SREBF1 at baseline were temporally associated with triglyceride at follow-up in only monozygotic twins. We then performed a mediation analysis with the longitudinal data and the result showed that the association between body mass index and HDL-C was partially mediated by the methylation level of cg06500161 (ABCG1), with a mediation proportion of 10.1%. CONCLUSIONS: Our study indicated that the DNA methylation levels of ABCG1, AKAP1 and SREBF1 may be involved in lipid metabolism and provided evidence for elucidating the regulatory mechanism of lipid homeostasis.
BACKGROUND: The associations between blood lipids and DNA methylation have been investigated in epigenome-wide association studies mainly among European ancestry populations. Several studies have explored the direction of the association using cross-sectional data, while evidence of longitudinal data is still lacking. RESULTS: We tested the associations between peripheral blood leukocytes DNA methylation and four lipid measures from Illumina 450 K or EPIC arrays in 1084 participants from the Chinese National Twin Registry and replicated the result in 988 participants from the China Kadoorie Biobank. A total of 23 associations of 19 CpG sites were identified, with 4 CpG sites located in or adjacent to 3 genes (TMEM49, SNX5/SNORD17 and CCDC7) being novel. Among the validated associations, we conducted a cross-lagged analysis to explore the temporal sequence and found temporal associations of methylation levels of 2 CpG sites with triglyceride and 2 CpG sites with high-density lipoprotein-cholesterol (HDL-C) in all twins. In addition, methylation levels of cg11024682 located in SREBF1 at baseline were temporally associated with triglyceride at follow-up in only monozygotic twins. We then performed a mediation analysis with the longitudinal data and the result showed that the association between body mass index and HDL-C was partially mediated by the methylation level of cg06500161 (ABCG1), with a mediation proportion of 10.1%. CONCLUSIONS: Our study indicated that the DNA methylation levels of ABCG1, AKAP1 and SREBF1 may be involved in lipid metabolism and provided evidence for elucidating the regulatory mechanism of lipid homeostasis.
Authors: Kim V E Braun; Klodian Dhana; Paul S de Vries; Trudy Voortman; Joyce B J van Meurs; Andre G Uitterlinden; Albert Hofman; Frank B Hu; Oscar H Franco; Abbas Dehghan Journal: Clin Epigenetics Date: 2017-02-07 Impact factor: 6.551
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