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Identifying causal pathways to disease using DNA methylation derived scores.

  • Full or part time
  • Application Deadline
    Monday, November 25, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

The University of Bristol is offering a 3.5 year full time PhD in research around Population Health to start in 2020. This studentship is funded through GW4 BioMed MRC Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£15,009 p.a. for 2019/20, updated each year). Additional research training and support funding of up to £5,000 per annum is also available.

Additional research and training funding is available over the course of the programme. This will cover costs such as research consumables, courses, conferences and travel. Additional competitive funds are available for high-cost training/research. The studentship is based at the Bristol Medical School (http://www.bristol.ac.uk/medical-school/).

This studentship will provide cross-disciplinary training in state-of-the-art genetic and genomic epidemiological approaches (under the supervision of Dr. Josine Min and Prof Caroline Relton at the MRC Integrative Epidemiology Unit, at the University of Bristol and Prof Jon Mill and Dr. Eilis Hannon at the University of Exeter Medical School - http://medicine.exeter.ac.uk/medical-school/) to address questions about the molecular mechanism underlying established disease risk factors. The student will combine epigenetic, genetic and causal inference analyses in large-scale epidemiological datasets.

Background:

To date the majority of studies used to link behavioral phenotypes such as cigarette smoking, and alcohol use to health outcomes typically employ questionnaire data. Multiple DNA methylation (DNAm) sites are strongly associated with (behavioural) traits. DNAm derived scores have been used to predict (or proxy for) these traits providing greater precision and biological proximity than self-reported measures (1). The DNAm derived smoking score is a widely used biomarker of lifetime exposure to tobacco smoke and may explain the molecular mechanism of the long-term risk of diseases following smoking cessation. There is growing interest in conducting genome-wide association studies (GWAS) and Mendelian randomization (https://www.youtube.com/watch?v=LoTgfGotaQ4) analysis on DNAm scores to identify novel genetic and causal factors influencing behavioural traits.

Aim and approach:

The overall aim of this PhD is to identify genetic variants and biological pathways associated with disease risk factors using DNAm scores. The specific risk factors/diseases for this project would depend on the candidate's research interests, but could include cell counts, smoking or alcohol use. The Genetics of DNA Methylation Consortium (GoDMC; http://www.godmc.org.uk/) has collected genetic and DNAm data across multiple cohorts offering the student an excellent platform for these analyses.

Methods:
1) Novel methodology can be used (and potentially developed) to construct DNAm scores on disease risk factors
2) GWAS on DNAm derived phenotype datasets will be conducted followed by meta-analyses. There will be several challenges with this type of analysis including heterogeneity of datasets in age, sex and tissue type.
3) To understand what aspect of the phenotype is captured by the DNAm phenotype, GWAS meta-analysis results will be compared to GWA results of detailed (self-reported) phenotypes (eg. in UK Biobank) and methylation quantitative loci from blood and brain.
4) MR analysis will be used to investigate causal relationships between DNAm derived measures and self-reported measures and other diseases/risk factors.
5) The heritability component of DNAm derived phenotypes will be estimated.

Environment

The student will be offered an excellent training in (epi)genetic epidemiology and will develop a unique range of skills incorporating (epi)genetic, and causal inference analyses which are highly relevant in the era of big data science. The student will have a possibility to develop his/her leadership skills, write manuscripts and report at scientific meetings. The student will be part of the MRC Integrative Epidemiology Unit (http://www.bristol.ac.uk/integrative-epidemiology/) at the University of Bristol which conducts some of the UK's most advanced population health science research and has access to high profile seminars, short courses (http://www.bristol.ac.uk/medical-school/study/short-courses/), HPC facilities (https://www.bristol.ac.uk/acrc/).

1. doi.org/10.1161/CIRCGENETICS.116.001506

Candidate requirements: Applications are welcome from high performing individuals across a wide range of disciplines closely related to natural sciences, biostatistics, genetics, bioinformatics, and computer science who have, or are expected to obtain, a 2.1 or higher degree. Applications are particularly welcome from individuals with a relevant research Masters degree.

How to apply:

Please make an online application for this project here: https://www.findaphd.com/phds/program/the-gw4-biomed-mrc-dtp-is-offering-up-to-18-fully-funded-studentships-across-a-range-of-biomedical-disciplines-with-a-start-date-of-october-2020/?p2940
Closing date: 5pm, 25th November 2019
Contact: Dr. Josine Min

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