BACKGROUND: DNA methylation is an essential nuclear process associated with genomic functions such as transcription factor binding and the regulation of gene expression. DNA methylation patterns can also serve as potential biomarkers for disease progression and response to therapy. However, the full dynamics of DNA methylation across daily physiologic events have not been fully elucidated. OBJECTIVE: We sought to study how ingesting a standardized meal acutely affects peripheral blood DNA methylation. DESIGN: We performed an observational study in healthy men (n = 26) on DNA methylation and gene expression in whole blood before and 160 min after the ingestion of a standardized meal. Cytosine-phosphate-guanine (CpG) methylation was assayed on the HumanMethylation450k microarray, and gene expression was measured with the Human Gene 2.1 ST Array. RESULTS: Differential methylation after food intake was detected in 13% of the analyzed probes (63,207 CpG probes) at a 5% false discovery rate (FDR). This effect was driven by changes in leukocyte fractions as estimated from comparisons against methylation datasets generated from sorted leukocytes. When methylation values were adjusted for estimated leukocyte fractions, 541 probes were observed to be altered in the postprandial state (5% FDR). CONCLUSIONS: Apparent alterations in DNA methylation 160 min after meal ingestion mainly reflect changes in the estimated leukocyte population in whole blood. These results have major methodologic implications for genome-wide methylation studies because they highlight the strong underlying effects of changes in leukocyte fractions on CpG methylation patterns as well as the potential importance of meal-standardized sampling procedures for future investigations when alterations in white blood cell fractions are unavailable. This trial was registered at clinicaltrials.gov as LSF008786.
BACKGROUND: DNA methylation is an essential nuclear process associated with genomic functions such as transcription factor binding and the regulation of gene expression. DNA methylation patterns can also serve as potential biomarkers for disease progression and response to therapy. However, the full dynamics of DNA methylation across daily physiologic events have not been fully elucidated. OBJECTIVE: We sought to study how ingesting a standardized meal acutely affects peripheral blood DNA methylation. DESIGN: We performed an observational study in healthy men (n = 26) on DNA methylation and gene expression in whole blood before and 160 min after the ingestion of a standardized meal. Cytosine-phosphate-guanine (CpG) methylation was assayed on the HumanMethylation450k microarray, and gene expression was measured with the Human Gene 2.1 ST Array. RESULTS: Differential methylation after food intake was detected in 13% of the analyzed probes (63,207 CpG probes) at a 5% false discovery rate (FDR). This effect was driven by changes in leukocyte fractions as estimated from comparisons against methylation datasets generated from sorted leukocytes. When methylation values were adjusted for estimated leukocyte fractions, 541 probes were observed to be altered in the postprandial state (5% FDR). CONCLUSIONS: Apparent alterations in DNA methylation 160 min after meal ingestion mainly reflect changes in the estimated leukocyte population in whole blood. These results have major methodologic implications for genome-wide methylation studies because they highlight the strong underlying effects of changes in leukocyte fractions on CpG methylation patterns as well as the potential importance of meal-standardized sampling procedures for future investigations when alterations in white blood cell fractions are unavailable. This trial was registered at clinicaltrials.gov as LSF008786.
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Authors: Jun Liu; Elena Carnero-Montoro; Jenny van Dongen; Samantha Lent; Ivana Nedeljkovic; Symen Ligthart; Pei-Chien Tsai; Tiphaine C Martin; Pooja R Mandaviya; Rick Jansen; Marjolein J Peters; Liesbeth Duijts; Vincent W V Jaddoe; Henning Tiemeier; Janine F Felix; Gonneke Willemsen; Eco J C de Geus; Audrey Y Chu; Daniel Levy; Shih-Jen Hwang; Jan Bressler; Rahul Gondalia; Elias L Salfati; Christian Herder; Bertha A Hidalgo; Toshiko Tanaka; Ann Zenobia Moore; Rozenn N Lemaitre; Min A Jhun; Jennifer A Smith; Nona Sotoodehnia; Stefania Bandinelli; Luigi Ferrucci; Donna K Arnett; Harald Grallert; Themistocles L Assimes; Lifang Hou; Andrea Baccarelli; Eric A Whitsel; Ko Willems van Dijk; Najaf Amin; André G Uitterlinden; Eric J G Sijbrands; Oscar H Franco; Abbas Dehghan; Tim D Spector; Josée Dupuis; Marie-France Hivert; Jerome I Rotter; James B Meigs; James S Pankow; Joyce B J van Meurs; Aaron Isaacs; Dorret I Boomsma; Jordana T Bell; Ayşe Demirkan; Cornelia M van Duijn Journal: Nat Commun Date: 2019-06-13 Impact factor: 14.919
Authors: Andreas Chatzittofis; Adrian Desai E Boström; Diana M Ciuculete; Katarina Görts Öberg; Stefan Arver; Helgi B Schiöth; Jussi Jokinen Journal: Sci Rep Date: 2021-10-11 Impact factor: 4.379
Authors: Adrian E Boström; Andreas Chatzittofis; Diana-Maria Ciuculete; John N Flanagan; Regina Krattinger; Marcus Bandstein; Jessica Mwinyi; Gerd A Kullak-Ublick; Katarina Görts Öberg; Stefan Arver; Helgi B Schiöth; Jussi Jokinen Journal: Epigenetics Date: 2019-09-22 Impact factor: 4.528