An investigation into DNA methylation patterns associated with risk preference in older individuals

Risk preference is a complex trait governed by psycho-social, environmental and genetic determinants. We aimed to examine how an individual’s risk preference associates with their epigenetic profile. Risk preferences were ascertained by asking participants of the Northern Ireland COhort for the Longitudinal study of Ageing to make a series of choices between hypothetical income scenarios. From these, four risk preference categories were derived, ranging from risk-averse to risk-seeking. Illumina’s Infinium High-Density Methylation Assay was used to evaluate the status of 862,927 CpGs. Risk preference and DNA methylation data were obtained for 1,656 individuals. The distribution of single-site DNA methylation levels between risk-averse and risk-seeking individuals was assessed whilst adjusting for age, sex and peripheral white cell counts. In this discovery cohort, 55 CpGs were identified with significantly different levels of methylation (p≤x10(−5)) between risk-averse and risk-seeking individuals when adjusting for the maximum number of covariates. No CpGs were significantly differentially methylated in any of the risk preference groups at an epigenome-wide association level (p<9x10(−8)) following covariate adjustment. Protein-coding genes NWD1 and LRP1 were among the genes in which the top-ranked dmCpGs were located for all analyses conducted. Mutations in these genes have previously been linked to neurological conditions. Epigenetic modifications have not previously been linked to risk-aversion using a population cohort, but may represent important biomarkers of accumulated, complex determinants of this trait. Several striking results from this study support further analysis of DNA methylation as an important link between measurable biomarkers and health behaviours.