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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Dna Methylation ; Alcohol ; Diet ; Epigenetic Clock ; Epigenetics ; Lifestyle Score ; Physical Activity ; Smoking
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2022
Prepublished im Jahr
HGF-Berichtsjahr
2022
ISSN (print) / ISBN
2001-1326
e-ISSN
2001-1326
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 12,
Heft: 6,
Seiten: ,
Artikelnummer: e851
Supplement: ,
Reihe
Verlag
Springer
Verlagsort
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF Topic(s)
30201 - Metabolic Health
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-506501-001
G-506500-001
Förderungen
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
Copyright
Erfassungsdatum
2022-07-08