PT - JOURNAL ARTICLE AU - Hamilton, Olivia KL AU - Zhang, Qian AU - McRae, Allan F AU - Walker, Rosie M AU - Morris, Stewart W AU - Redmond, Paul AU - Campbell, Archie AU - Murray, Alison D AU - Porteous, David J AU - Evans, Kathryn L AU - McIntosh, Andrew M AU - Deary, Ian J AU - Marioni, Riccardo E TI - An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort 1936 AID - 10.1101/278234 DP - 2018 Jan 01 TA - bioRxiv PG - 278234 4099 - http://biorxiv.org/content/early/2018/03/09/278234.short 4100 - http://biorxiv.org/content/early/2018/03/09/278234.full AB - 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.