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Is disease risk conferred during childhood set in stone? Using genetics to understand how modifiable lifestyle changes can help prevent disease in later life

  • 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 2019. 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 MRC Integrative Epidemiology Unit (IEU) (http://www.bristol.ac.uk/integrative-epidemiology/) at the Bristol Medical School. For further information please see http://www.bristol.ac.uk/integrative-epidemiology/ and http://www.bristol.ac.uk/medical-school/.

This is cross-disciplinary project that provides a unique opportunity at the interface of data science, genetics and epidemiology. You will be supervised by Dr Tom Richardson (MRC Integrative Epidemiology Unit [IEU], Univ. Bristol), Prof. George Davey Smith (MRC IEU, Univ. Bristol), Prof. Tim Frayling (Univ. Exeter) and Dr Jess Tyrrell (Univ. Exeter).

Background:

Understanding the manner in which modifiable factors (including lifestyle) during childhood and adolescence influence our risk of disease is challenging. For instance, individuals who are obese in early life have elevated risk of cardiovascular disease. However, as these individuals tend to remain obese into later life, it is unclear how much of this conferred risk can be reversed by making lifestyle changes. Furthermore, complex disease is typically determined by multiple risk factors, which may or may not act independently of one and other.

In this PhD project the student will use large datasets (such as the UK Biobank and ALSPAC cohorts) to develop a putative causal map of how multiple lifestyle factors influence disease risk. There will be an emphasis on early life exposures, as results suggesting that conferred risk during childhood can be reversed will have an important translatable message that can impact social policy. Conversely, it is imperative to better understand which early life risk factors have an immutable influence on disease susceptibility which cannot be mitigated through lifestyle modifications. The student will apply the principles of a technique in epidemiology known as Mendelian randomization (MR). This approach uses genetics to disentangle causal relationships, which is particularly powerful given that our genes are inherited randomly at birth. As such they are robust to factors such as confounding and reverse causation which hinder observational analyses.

For example, we recently used MR to separate childhood BMI from adult BMI, something that is very hard to do without genetic data. This study demonstrated that increased risk of cardiovascular disease and type 2 diabetes attributed to childhood obesity can be mitigated if individuals reduce their body mass index (BMI) (Richardson et al (2019)). In contrast, our MR analyses indicate that higher early life BMI has a more direct influence on risk of diseases such as breast cancer, which we postulate may be due to earlier onset of puberty (and/or adulthood weight gain).

Aim and approach:

1) Undertake genome-wide association studies to identify genetic variants robustly associated with early life risk factors. We will start with metabolic traits (e.g. BMI, blood pressure, lipids) although there is scope to investigate other traits during the PhD (such as glycemic traits, psychiatric/neurological traits and molecular markers).
2) Use these findings to infer whether early life risk factors have a direct effect on disease risk in later life using MR. For example, we hypothesise that a higher BMI during childhood has a direct effect on risk of anorexia due to social pressures, whereas its influence on risk of depression is less well understood. Findings in this area could therefore have important translatable implications for social policy.

Environment

The PhD student will be predominantly based at the MRC IEU in Bristol (with supervisors Davey Smith and Richardson), where they will join a vibrant, supportive cohort of students funded by various funding schemes (including the MRC, British Heart Foundation (BHF) and Wellcome Trust) undertaking like-minded research. Before starting their PhD project, they will have the opportunity to undertake a short-term project (~3 months in length) with a researcher at the IEU, which will help them to develop skills applicable to their main project. During their first year, they will attend short courses (http://www.bristol.ac.uk/medical-school/study/short-courses/) hosted by the Population Health Sciences Institute which are attended by researchers from across the world. They will also be encouraged to attend external workshops, seminars and conferences throughout the project to acquire and develop new skills and knowledge which will benefit them throughout their PhD and future career.

There will be opportunities to visit Professor Frayling and Dr Tyrrell’s dynamic research team at the Exeter Medical School to benefit from their wealth of relevant knowledge to this PhD project. Finally, there is scope to visit industry partners to gain further experience in working with leading scientists in the field which should be particularly valuable with respect to translating research findings.

Candidate requirements: Applications are welcome from high performing individuals across a wide range of disciplines closely related to natural sciences, biostatistics, genetics, bio-chemistry, mathematics 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:

You can apply for the studentship through the MRC GW4 BioMed DTP web site (https://www.gw4biomed.ac.uk/doctoral-students/) until 5pm on Monday 25th November 2019.

Contact: Tom Richardson ()

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