Qihua Tan1,2, Bastiaan T Heijmans3, Jacob V B Hjelmborg4, Mette Soerensen4,2, Kaare Christensen4,2, Lene Christiansen4. 1. Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense C, Denmark, qtan@health.sdu.dk. 2. Unit of Human Genetics, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense C, Denmark and. 3. Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands. 4. Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense C, Denmark.
Abstract
BACKGROUND: Current epigenetic studies on aging are dominated by the cross-sectional design that correlates subjects' ages or age groups with their measured epigenetic profiles. Such studies have been more aimed at age prediction or building up the epigenetic clock of age rather than focusing on the dynamic patterns in epigenetic changes during the aging process. METHODS: We performed an epigenome-wide association study of intra-individual longitudinal changes in DNA methylation at CpG (cytosine-phosphate-guanine) sites measured in whole-blood samples of a cohort of 43 elderly twin pairs followed for 10 years (age at intake 73-82 years). Biological pathway analysis and survival analysis were also conducted on CpGs showing longitudinal change in their DNA-methylation levels. Classical twin models were fitted to each CpG site to estimate the genetic and environmental effects on DNA-methylation. RESULTS: Our analysis identified 2284 CpG sites whose DNA-methylation levels changed longitudinally over the follow-up. Twin modelling revealed that the longitudinal change for 90% of these CpG sites was explained solely by individual unique environmental factors and only for 10% of these sites was it influenced by familial factors (genetic or shared environment). Over 60% of the identified CpG sites were replicated (same direction and replication P < 0.05) in an independent cross-sectional sample of 300 twins aged from 30 to 74 years. The replication rate went up to 91% for the top 53 CpGs with P < 1 × 10-07. Pathway analysis of genes linked to these CpGs identified biologically meaningful gene-sets involved in cellular-signalling events and in transmission across chemical synapses, which are important molecular underpinnings of aging-related degenerative disorders. CONCLUSION: Our epigenome-wide association studies on a cohort of old twins followed up for 10 years identified highly replicable epigenetic biomarkers predominantly implicated in signalling pathways of degenerative disorders and survival in the elderly.
BACKGROUND: Current epigenetic studies on aging are dominated by the cross-sectional design that correlates subjects' ages or age groups with their measured epigenetic profiles. Such studies have been more aimed at age prediction or building up the epigenetic clock of age rather than focusing on the dynamic patterns in epigenetic changes during the aging process. METHODS: We performed an epigenome-wide association study of intra-individual longitudinal changes in DNA methylation at CpG (cytosine-phosphate-guanine) sites measured in whole-blood samples of a cohort of 43 elderly twin pairs followed for 10 years (age at intake 73-82 years). Biological pathway analysis and survival analysis were also conducted on CpGs showing longitudinal change in their DNA-methylation levels. Classical twin models were fitted to each CpG site to estimate the genetic and environmental effects on DNA-methylation. RESULTS: Our analysis identified 2284 CpG sites whose DNA-methylation levels changed longitudinally over the follow-up. Twin modelling revealed that the longitudinal change for 90% of these CpG sites was explained solely by individual unique environmental factors and only for 10% of these sites was it influenced by familial factors (genetic or shared environment). Over 60% of the identified CpG sites were replicated (same direction and replication P < 0.05) in an independent cross-sectional sample of 300 twins aged from 30 to 74 years. The replication rate went up to 91% for the top 53 CpGs with P < 1 × 10-07. Pathway analysis of genes linked to these CpGs identified biologically meaningful gene-sets involved in cellular-signalling events and in transmission across chemical synapses, which are important molecular underpinnings of aging-related degenerative disorders. CONCLUSION: Our epigenome-wide association studies on a cohort of old twins followed up for 10 years identified highly replicable epigenetic biomarkers predominantly implicated in signalling pathways of degenerative disorders and survival in the elderly.
Authors: Cristina M Lanata; Joanne Nititham; Kimberly E Taylor; Olivia Solomon; Sharon A Chung; Ashira Blazer; Laura Trupin; Patricia Katz; Maria Dall'Era; Jinoos Yazdany; Marina Sirota; Lisa F Barcellos; Lindsey A Criswell Journal: Arthritis Rheumatol Date: 2022-09-01 Impact factor: 15.483
Authors: Ernesto Miranda-Morales; Karin Meier; Ada Sandoval-Carrillo; José Salas-Pacheco; Paola Vázquez-Cárdenas; Oscar Arias-Carrión Journal: Front Mol Neurosci Date: 2017-07-18 Impact factor: 5.639