Abstract
Genome-wide DNA methylation has been implicated in complex human diseases. Here, we identified epigenetic biomarkers for type 2 diabetes (T2D) underlying obesogenic environments. In a blood-based DNA methylation analysis of 11 monozygotic twins (MZTW) discordant for T2D, we discovered genetically independent candidate methylation sites. In a follow-up replication study (17 MZTW pairs) for external validation, we replicated the T2D-association at a novel CpG signal in the ELOVL fatty acid elongase 5 (ELOVL5) gene specific to T2D-discordant MZTW. For concordant DNA methylation signatures in tissues, we further confirmed that a CpG site (cg18681426) was associated with adipogenic differentiation between human preadipocytes and adipocytes isolated from the same biopsy sample. In addition, the ELOVL5 gene was significantly differentially expressed in adipose tissues from unrelated T2D patients and in human pancreatic islets. Our results demonstrate that blood-derived DNA methylation is associated with T2D risk as a proxy for cumulative epigenetic status in human adipose and pancreatic tissues. Moreover, ELOVL5 expression was increased in cellular and mouse models of induced obesity-related diabetes. These findings may provide new insights into epigenetic architecture by uncovering methylation-based biomarkers.
Highlights
Genome-wide DNA methylation has been implicated in complex human diseases
To elucidate the impact of blood-derived epigenetic differences on human tissues, we further evaluated the CpG site in ELOVL5 and its relationship to altered DNA methylomic profiles between preadipocytes and adipocytes isolated from adipose tissue from the same individual (Fig. S2)
Epigenome-wide approaches by Ling et al identified altered DNA methylation[15,25,26,27] and blood-derived biomarkers associated with insulin secretion and type 2 diabetes (T2D) in human pancreatic islets[18]
Summary
Genome-wide DNA methylation has been implicated in complex human diseases. Here, we identified epigenetic biomarkers for type 2 diabetes (T2D) underlying obesogenic environments. Our results demonstrate that blood-derived DNA methylation is associated with T2D risk as a proxy for cumulative epigenetic status in human adipose and pancreatic tissues. ELOVL5 expression was increased in cellular and mouse models of induced obesity-related diabetes These findings may provide new insights into epigenetic architecture by uncovering methylation-based biomarkers. Epigenome-wide association studies (EWAS) have identified epigenetic markers for phenotypic consequences underlying cumulative environmental changes using disease-discordant monozygotic twin (MZTW) models[8,9,10,11,12]. An epigenomic analysis of the blood-derived DNA methylome demonstrated T2D-associated genetically independent differentially methylated regions (giDMRs) in MZTW13. We investigated ELOVL5 expression in human liver cells and in tissues from mice with induced obesity-related diabetes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
