DNA methylation patterns reflect individual's lifestyle independent of obesity

Ireen Klemp; Anne Hoffmann; Luise Müller; Tobias Hagemann; Kathrin Horn; Kerstin Rohde‐Zimmermann; Anke Tönjes; Joachim Thiery; Markus Löffler; Ralph Burkhardt; Yvonne Böttcher; Michael Stumvoll; Matthias Blüher; Knut Krohn; Markus Scholz; Ronny Baber; Paul W Franks; Peter Kovacs; Maria Keller

doi:10.1002/ctm2.851

Clinical and Translational Medicine (Jun 2022)

DNA methylation patterns reflect individual's lifestyle independent of obesity

Ireen Klemp,
Anne Hoffmann,
Luise Müller,
Tobias Hagemann,
Kathrin Horn,
Kerstin Rohde‐Zimmermann,
Anke Tönjes,
Joachim Thiery,
Markus Löffler,
Ralph Burkhardt,
Yvonne Böttcher,
Michael Stumvoll,
Matthias Blüher,
Knut Krohn,
Markus Scholz,
Ronny Baber,
Paul W Franks,
Peter Kovacs,
Maria Keller

Affiliations

Ireen Klemp: Medical Department III—Endocrinology, Nephrology, Rheumatology University of Leipzig Medical Center Leipzig Germany
Anne Hoffmann: Helmholtz Institute for Metabolic Obesity and Vascular Research (HI‐MAG), Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig Leipzig Germany
Luise Müller: Medical Department III—Endocrinology, Nephrology, Rheumatology University of Leipzig Medical Center Leipzig Germany
Tobias Hagemann: Helmholtz Institute for Metabolic Obesity and Vascular Research (HI‐MAG), Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig Leipzig Germany
Kathrin Horn: Institute for Medical Informatics, Statistics and Epidemiology University of Leipzig Leipzig Germany
Kerstin Rohde‐Zimmermann: Medical Department III—Endocrinology, Nephrology, Rheumatology University of Leipzig Medical Center Leipzig Germany
Anke Tönjes: Medical Department III—Endocrinology, Nephrology, Rheumatology University of Leipzig Medical Center Leipzig Germany
Joachim Thiery: Medical Faculty University of Kiel Kiel Germany
Markus Löffler: Institute for Medical Informatics, Statistics and Epidemiology University of Leipzig Leipzig Germany
Ralph Burkhardt: Institute of Clinical Chemistry and Laboratory Medicine University Hospital Regensburg Regensburg Germany
Yvonne Böttcher: Department of Clinical Molecular Biology Institute of Clinical Medicine University of Oslo Oslo Norway
Michael Stumvoll: Medical Department III—Endocrinology, Nephrology, Rheumatology University of Leipzig Medical Center Leipzig Germany
Matthias Blüher: Medical Department III—Endocrinology, Nephrology, Rheumatology University of Leipzig Medical Center Leipzig Germany
Knut Krohn: Medical Faculty University of Leipzig Leipzig Germany
Markus Scholz: Institute for Medical Informatics, Statistics and Epidemiology University of Leipzig Leipzig Germany
Ronny Baber: Medical Faculty University of Leipzig Leipzig Germany
Paul W Franks: Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences Lund University Skåne University Hospital Malmö Sweden
Peter Kovacs: Medical Department III—Endocrinology, Nephrology, Rheumatology University of Leipzig Medical Center Leipzig Germany
Maria Keller: Medical Department III—Endocrinology, Nephrology, Rheumatology University of Leipzig Medical Center Leipzig Germany

DOI: https://doi.org/10.1002/ctm2.851
Journal volume & issue: Vol. 12, no. 6
pp. n/a – n/a

Abstract

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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 (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.

Published in Clinical and Translational Medicine

ISSN: 2001-1326 (Online)
Publisher: Wiley
Country of publisher: Australia
LCC subjects: Medicine: Medicine (General)
Website: https://onlinelibrary.wiley.com/journal/20011326

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