Open AccessDNA methylation patterns reflect individual's lifestyle independent of obesity
Author(s) -
Klemp Ireen,
Hoffmann Anne,
Müller Luise,
Hagemann Tobias,
Horn Kathrin,
RohdeZimmermann 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
Publication year - 2022
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.851
Subject(s) - dna methylation , methylation , body mass index , epigenetics , medicine , cohort , population , oncology , genetics , biology , bioinformatics , physiology , gene , gene expression , environmental health
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.