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Using genetics to explore patterns of change in weight and height during key life course periods on subsequent health outcomes


About This PhD Project

Project Description

3/4-year PhD starting in October 2019. Closing date: 5pm, 1st May 2019.

We are offering an exciting PhD opportunity for candidates interested in using innovative statistical methods to investigate the causal role of pubertal growth on health outcomes in adulthood. The successful candidate will benefit from a highly multidisciplinary supervisory team and research training environment in the MRC Integrative Epidemiology Unit: http://www.bristol.ac.uk/integrative-epidemiology/

This 3- or 4-year studentship* is ideal for a talented computer scientist wishing to develop strong interdisciplinary skills at the interface of Computer Science and Digital Health. We offer a fully-funded studentship (starting between April and October 2019). This will be based in the MRC Integrative Epidemiology Unit at the University of Bristol, a leading centre for research excellence in population health science. The successful candidate will have access to an excellent training portfolio of short courses and transferable skills training and be part of a cross-disciplinary cohort of PhD students.

The successful applicant will be supervised by Prof Deborah A Lawlor (http://www.bristol.ac.uk/social-community-medicine/people/debbie-a-lawlor/index.html) and Prof Kate Tilling (http://www.bristol.ac.uk/social-community-medicine/people/kate-m-tilling/index.html) from the University of Bristol and Dr Nicole Warrington (https://researchers.uq.edu.au/researcher/8867) from the University of Queensland. If you are interested please get in touch with one of us for an informal chat.

* Depending on the qualifications, experience and skills of the person offered the studentship this will be a 4- (1 + 3) year or 3-year studentship. If offered as 4-year studentship the student will complete 3 ‘mini-projects’ in different areas to develop their multidisciplinary skills before starting their main PhD project.

Summary

Complex developmental processes regulate changes in height and weight across childhood and adolescence. Distinct growth patterns during puberty are correlated with adverse health outcomes on later life including poor cardio-metabolic health (e.g. diabetes, hypertension and heart attacks). However, the genetic mechanisms mediating differences in growth trajectories during childhood and adolescence remain largely unknown.

The central aims of this PhD are to:

1. Summarize complex longitudinal height and weight growth trajectories into parameters that can be used in a genome-wide association study. Of particular interest will be the timings of adiposity rebound (generally between 5 and 6 years of age) and pubertal transition. As part of this aim, you will explore a range of cutting-edge statistical methods and determine which method provides the best summary of the data. The chosen method will then be applied to up to 20 cohorts in the Early Growth Genetics (EGG) Consortium (https://egg-consortium.org/) to identify novel genetic variants associated with these growth trajectories.

2. Subsequently use the genetic variants identified in the genome-wide association study to determine the extent to which adiposity rebound and/or pubertal growth causes adverse cardio-metabolic health outcomes. If a causal relationship is identified, it will need to be confirmed that it is the growth trajectories that are causing adverse outcomes and not just height/weight at any age.

The above describes the broad aims. The successful student will also be encouraged to develop and pursue their own research interests. Possible directions include:
(i) exploring methods for incorporating longitudinal data in causal modelling, rather than using the data reduction techniques explored in aim 1 above. This could include methods such as structural equation modelling or other multivariable techniques.
(ii) although the supervisors have interests and expertise around cardio-metabolic outcomes there would be the potential to develop hypotheses around impacts of growth trajectories on later outcomes (e.g. pregnancy, perinatal, neurocognitive or mental health) and use MR to test causal effects of different growth patterns with these outcomes
iii) using MR to examine the causal risk factors for different height and weight trajectories, including maternal and offspring genetics.

You will use data from birth cohorts, including the world-leading Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, and UK Biobank. You will also collaborate with colleagues in the Early Growth Genetics (EGG) consortium to maximize the ability to detect regions of the genome associated with different growth patterns in particular those in relation to adiposity rebound and pubertal growth.

Applications must be completed online at http://www.bristol.ac.uk/study/postgraduate/apply, choosing “ Faculty of Health Sciences” and the “Population Health Sciences” PhD programme, and entering “MRC IEU” as the fee payer.
The studentship offers a stipend at standard MRC rates (£14,777 in 2018/19), covers the cost of UK tuition fees and provides £1000 per year training costs. Standard MRC eligibility criteria apply. Only applicants from the EU and UK are eligible for this programme.

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