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Int J Obes (Lond). 2019 Mar 6. doi: 10.1038/s41366-018-0262-3. [Epub ahead of print]

An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort.

Author information

1
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
2
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK.
3
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
4
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
5
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
6
Aberdeen Biomedical Imaging Centre, Lilian Sutton Building, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
7
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, UK.
8
Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK.
9
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. Riccardo.Marioni@ed.ac.uk.
10
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. Riccardo.Marioni@ed.ac.uk.

Abstract

BACKGROUND:

The relationship between obesity and adverse health is well established, but little is known about the contribution of DNA methylation to obesity-related health outcomes. This study tests associations between an epigenetic score for body mass index (BMI) and health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian Birth Cohort 1936. This study also tests whether these associations are independent of phenotypic BMI.

METHOD:

Analyses were conducted using data from the Lothian Birth Cohort 1936 (n = 892). Weights for the epigenetic BMI score were derived using penalised regression on methylation data from unrelated Generation Scotland participants (n = 2562). Associations were tested for replication in an independent sample: the Lothian Birth Cohort 1921 (n = 433).

RESULTS:

A higher epigenetic BMI score was associated with higher BMI (R2 = 0.1), greater body weight (R2 = 0.06), greater time taken to walk 6 m, poorer lung function and poorer general physical health (all R2 = 0.02), greater levels of triglycerides (R2 = 0.09), greater %total HbA1c (R2 = 0.06), lower levels of high-density lipoprotein cholesterol (HDL; R2 = 0.08), higher HDL ratio (HDL/total cholesterol; R2 = 0.03), lower health-related quality of life, physical inactivity, and greater social deprivation (all R2 = 0.02). The epigenetic BMI score (per SD) was also associated with type 2 diabetes (OR 2.17, 95% CI 1.67, 2.84), cardiovascular disease (OR 1.45, 95% CI 1.24, 1.71) and high blood pressure (OR 1.30, 95% CI 1.13, 1.49; all p < 0.00026 after Bonferroni correction). Associations were replicated for BMI (R2 = 0.06), body weight (R2 = 0.04), health-related quality of life (R2 = 0.02), HbA1c (R2 = 0.07) and triglycerides (R2 = 0.07; all p < 0.0045 after Bonferroni correction).

CONCLUSIONS:

We observed and replicated associations between an epigenetic score for BMI and variables related to poor physical health and metabolic syndrome. Regression models with both epigenetic and phenotypic BMI scores as predictors accounted for a greater proportion of variance in all outcome variables than either predictor alone, demonstrating independent and additive effects of epigenetic and phenotypic BMI scores.

PMID:
30842548
DOI:
10.1038/s41366-018-0262-3

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