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Epigenetic prediction of complex traits and death
Daniel L McCartney,
Anna J Stevenson,
Stuart J Ritchie,
Rosie M Walker,
Stewart W Morris,
Alison D Murray,
Heather C Whalley,
Catharine R Gale,
David J Porteous,
Chris S Haley,
Allan F. McRae,
Naomi R. Wray,
Peter M. Visscher,
Andrew M McIntosh,
Kathryn L Evans,
Ian J Deary,
Riccardo E Marioni
Posted 03 Apr 2018
bioRxiv DOI: 10.1101/294116 (published DOI: 10.1186/s13059-018-1514-1)
Posted 03 Apr 2018
Background: Genome-wide DNA methylation (DNAm) profiling has allowed for the development of molecular predictors for a multitude of traits and diseases. Such predictors may be more accurate than the self-reported phenotypes, and could have clinical applications. Here, penalised regression models were used to develop DNAm predictors for body mass index (BMI), smoking status, alcohol consumption, and educational attainment in a cohort of 5,100 individuals. Using an independent test cohort comprising 906 individuals, the proportion of phenotypic variance explained in each trait was examined for DNAm-based and genetic predictors. Receiver operator characteristic curves were generated to investigate the predictive performance of DNAm-based predictors, using dichotomised phenotypes. The relationship between DNAm scores and all-cause mortality (n = 214 events) was assessed via Cox proportional-hazards models. Results: The DNAm-based predictors explained different proportions of the phenotypic variance for BMI (12%), smoking (60%), alcohol consumption (12%) and education (3%). The combined genetic and DNAm predictors explained 20% of the variance in BMI, 61% in smoking, 13% in alcohol consumption, and 6% in education. DNAm predictors for smoking, alcohol, and education but not BMI predicted mortality in univariate models. The predictors showed moderate discrimination of obesity (AUC=0.67) and alcohol consumption (AUC=0.75), and excellent discrimination of current smoking status (AUC=0.98). There was poorer discrimination of college-educated individuals (AUC=0.59). Conclusions: DNAm predictors correlate with lifestyle factors that are associated with health and mortality. They may supplement DNAm-based predictors of age to identify the lifestyle profiles of individuals and predict disease risk.
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