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 Infinium⃝R 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 dif- ferences (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 individu- als. 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 guid- ance (adj. p < .05). We showed that methylation age correlates with chronological age and waist-to-hip ratio with lower DNA methylation age (DNAmAge) acceler- ation 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 differ- ences derived from obesity.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:90514 |
| Date | 14 March 2024 |
| Creators | Klemp, Ireen |
| Contributors | Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 10.1002/ctm2.851, 10.1002/ctm2.851 |
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