The overall aim of this proposal is to develop statistical methods and paradigms to better leverage the considerable amount of peripheral blood DNA methylation data that has been (and will be) collected from large scale epidemiological studies. In particular, our focus is on developing and optimizing statistical methods of using DNA methylation profiles to "tag" environmental exposures, so that this information can be better utilized to investigate the genetic and environmental basis of complex traits and diseases.

The specific aims of the proposal are:

Aim 1: To assess the degree to which medically relevant environmental exposures can be tagged by DNA methylation profiles from peripheral blood and to investigate the ability of different statistical approaches to tag these exposures.

Aim 2: To investigate the degree to which "DeMendelization" of methylation profiles (i.e removing the effect of genetic variants) can improve tagging of environmental exposures.

Aim 3: To investigate whether genome-wide association meta-analyses of methylation profiles that index environmental exposures could be used to identify genetic variants underlying medically relevant exposures known to have a heritable component.