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An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort 1936.

By Olivia KL Hamilton, Qian Zhang, Allan F. McRae, Rosie M Walker, Stewart W Morris, Paul Redmond, Archie Campbell, Alison D Murray, David J Porteous, Kathryn L Evans, Andrew M McIntosh, Ian J Deary, Riccardo E Marioni

Posted 09 Mar 2018
bioRxiv DOI: 10.1101/278234 (published DOI: 10.1038/s41366-018-0262-3)

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. Additionally, it is of interest whether such contributions are independent of those attributed by the most widely used clinical measure of body mass: the Body Mass Index (BMI). Method: We tested whether an epigenetic BMI score accounts for inter-individual variation in health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian Birth Cohort 1936 (n=903). Weights for the epigenetic BMI score were derived using penalised regression on methylation data from unrelated Generation Scotland participants (n=2566). Results: The Epigenetic BMI score was associated with variables related to poor physical health (R2 ranges from 0.02-0.10), metabolic syndrome (R2 ranges from 0.01-0.09), lower crystallised intelligence (R2=0.01), lower health-related quality of life (R2=0.02), physical inactivity (R2=0.02), and social deprivation (R2=0.02). The epigenetic BMI score (per SD) was also associated with self-reported type 2 diabetes (OR 2.25, 95 % CI 1.74, 2.94), cardiovascular disease (OR 1.44, 95 % CI 1.23, 1.69) and high blood pressure (OR 1.21, 95% CI 1.13, 1.48; all at p<0.0011 after Bonferroni correction). Conclusions: Our results show that regression models with epigenetic and phenotypic BMI scores as predictors account for a greater proportion of all outcome variables than either predictor alone, demonstrating independent and additive effects of epigenetic and phenotypic BMI scores.

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