Biomarkers of health risk in DNA methylation

PhD project (3/4 yr research project leading to independent research at the doctorate level)

Matthew Suderman, Caroline Relton


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Rationale

Disease risk and outcome is often influenced by unseen factors such as past exposures and heredity. Many environmental exposures have associated health risks. Knowing the exposure history of an individual is often vital for selecting effective preventative interventions or treatments. Unfortunately assembled histories are often incomplete and imprecise and may even be missing or unreliable. Exposure outcomes differ between individuals and early warning signs may be difficult to observe.

Associations between DNA methylation measured in peripheral tissues and past environmental exposures as well as future health outcomes have been observed in numerous studies. In some cases, these associations are independent of known biomarkers or assembled exposure histories.

Aims & objectives

The aim of this project is to develop models of health risk using DNA methylation profiles from a variety of human cohort studies and findings reported in the DNA methylation literature. Models could ultimately have clinical application for improving disease risk assessment and/or treatment selection. There are multiple options for the specific diseases and outcomes to investigate as well as a variety of traits and exposures.

Methods

Model development will begin with a review of the literature to catalogue large-scale studies reporting associations in peripheral tissue DNA methylation with environmentally relevant exposures and disease risk or incidence. This review will be performed in collaboration with the research team building the Epigenome-wide Association Catalogue (EWAS Catalogue), a database to store all published associations with DNA methylation. Candidate genomic loci from this review will be used to build models of disease risk and of factors relevant to risk. Models will be built using DNA methylation profiles of human populations available in public repositories, housed locally at the and at other institutions with whom we currently have active collaborations.

References


Created on May 21, 2018, 2:31 p.m.

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