DNA methylation patterns reflect individual's lifestyle independent of obesity. Issue 6 (12th June 2022)

• Record Type: Journal Article
• Authors: Klemp, Ireen; Hoffmann, Anne; Müller, Luise; Hagemann, Tobias; Horn, Kathrin; Rohde‐Zimmermann, Kerstin; Tönjes, Anke; Thiery, Joachim; Löffler, Markus; Burkhardt, Ralph; Böttcher, Yvonne; Stumvoll, Michael; Blüher, Matthias; Krohn, Knut; Scholz, Markus; Baber, Ronny; Franks, Paul W; Kovacs, Peter; Keller, Maria
• Is Part Of: Clinical and translational medicine. Volume 12:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-12
• Subjects: alcohol -- diet -- DNA methylation -- epigenetic clock -- epigenetics -- lifestyle score -- physical activity -- smoking; Clinical medicine -- Periodicals; Medicine, Experimental -- Periodicals; Medical innovations -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 616.027
• DOI: 10.1002/ctm2.851
• Languages: English
• ISSNs: 2001-1326

Abstract

Abstract: Objective: Obesity is driven by modifiable lifestyle factors whose effects may be mediated by epigenetics. Therefore, we investigated lifestyle effects on blood DNA methylation in participants of the LIFE‐Adult study, a well‐characterised population‐based cohort from Germany. Research design and methods: Lifestyle scores (LS) based on diet, physical activity, smoking and alcohol intake were calculated in 4107 participants of the LIFE‐Adult study. Fifty subjects with an extremely healthy lifestyle and 50 with an extremely unhealthy lifestyle (5th and 95th percentiles LS) were selected for genome‐wide DNA methylation analysis in blood samples employing Illumina Infinium® Methylation EPIC BeadChip system technology. Results: Differences in DNA methylation patterns between body mass index groups (<25 vs. >30 kg/m 2 ) were rather marginal compared to inter‐lifestyle differences (0 vs. 145 differentially methylated positions [DMPs]), which identified 4682 differentially methylated regions (DMRs; false discovery rate [FDR <5%) annotated to 4426 unique genes. A DMR annotated to the glutamine‐fructose‐6‐phosphate transaminase 2 ( GFPT2 ) locus showed the strongest hypomethylation (∼6.9%), and one annotated to glutamate rich 1 ( ERICH1 ) showed the strongest hypermethylation (∼5.4%) in healthy compared to unhealthy lifestyle individuals. Intersection analysis showed that diet, physical activity, smoking and alcohol intake equally contributed to the observed differences, which affected, among others, pathways related to glutamatergic synapses (adj. p < .01) and axon guidance (adj. p < .05). We showed that methylation age correlates with chronological age and waist‐to‐hip ratio with lower DNA methylation age (DNAmAge) acceleration distances in participants with healthy lifestyles. Finally, two identified top DMPs for the alanyl aminopeptidase ( ANPEP ) locus also showed the strongest expression quantitative trait methylation in blood. Conclusions: DNA methylation patterns help discriminate individuals with a healthy versus unhealthy lifestyle, which may mask subtle methylation differences derived from obesity. Abstract : Long‐term lifestyle habits including diet, physical activity, smoking and alcohol consumption jointly shape epigenetic patterns and affect methylation age. These effects clearly dominate over those driven by age and obesity alone. An interplay of lifestyle aspects needs to be considered when analysing epigenetic data with regard to complex metabolic diseases.