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Klemp, I.* ; Hoffmann, A. ; Müller, L.* ; Hagemann, T. ; Horn, K.* ; Rohde-Zimmermann, K. ; Tönjes, A.* ; Thiery, J.* ; Löffler, M.* ; Burkhardt, R.* ; Böttcher, Y.* ; Stumvoll, M. ; Blüher, M. ; Krohn, K.* ; Scholz, M.* ; Baber, R.* ; Franks, P.W.* ; Kovacs, P.* ; Keller, M.

DNA methylation patterns reflect individual's lifestyle independent of obesity.

Clin. Transl. Med. 12:e851 (2022)

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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/m² ) 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Dna Methylation ; Alcohol ; Diet ; Epigenetic Clock ; Epigenetics ; Lifestyle Score ; Physical Activity ; Smoking

ISSN (print) / ISBN 2001-1326

e-ISSN 2001-1326

Journal Clinical and translational medicine

Quellenangaben Volume: 12, Issue: 6, Article Number: e851

Publisher Springer

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants European Regional Development Fund (ERDF)
European Union
Leipzig Research Center for Civilisation Diseases (LIFE)
Deutsches Zentrum fur Diabetesforschung
Free State of Saxony
German Diabetes Association
Medical Faculty of the University Leipzig