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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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