The MRC Integrative Epidemiology Unit at the University of Bristol is the leading group for the development and application of causal analysis and evidence triangulation in health research to improve lives. This student will be supported by an interdisciplinary team of academic staff who are experts in their fields. For more information about the MRC Integrative Epidemiology Unit and the PhD programme, please visit the website.
Rationale
Estimating the influence of genotypes and traits on fitness is a fundamental question in biology. While the question requires causal inference, many analytical frameworks (e.g. Price equation) are embedded in a statistical framework that are unable to separate cause from correlation. Mendelian randomisation is an analytical framework that is widely used in epidemiological studies, and we have shown it can be used in humans to make causal inference of traits on fitness. In this project we will investigate the theoretical properties of this approach and apply it to a vast array of genetic data to understand the landscape of the genotype-phenotype map on fitness. This mapping will allow us to make inference about critically important questions, such as the degree to which pleiotropy modulates directional selection, and the degree to which stabilising selection maintains natural genetic variation.
Aims and objectives
- One approach to estimate the influence of traits on fitness is to estimate the causal influences on reproductive traits such as fecundity, age of first menarche, age of first birth and age of menopause. We will investigate the way in which these traits approximate fitness, using multi-generation samples and latent modelling through genomic structural equation modelling
- We will perform an exhaustive scan of traits on measures of fitness determined from (1), to build a profile of the genotypes-trait-fitness landscape
- We will use (2) to model and infer the degree to which important mechanisms such as pleiotropy and trait network effects either accelerate or constrain directional selection, and to what degree they maintain natural genetic variation.
Methods
Throughout the project we will use a mixture of genome-wide association studies, a suite of methods developed for Mendelian randomisation, as well as theoretical and simulation analyses of selection processes.
University of Bristol, Bristol Medical School
Bristol Medical School is the largest and one of the most diverse Schools in the University of Bristol, with approximately 1100 members of staff, 1350 undergraduate, 250 postgraduate taught and 240 postgraduate doctoral research students. The Head of School is Professor Matt Hickman. The Medical School has two departments: Population Health Sciences and Translational Health Sciences. The School is a leading centre for research and teaching across these areas. Research in the School is collaborative and multi-disciplinary, with staff coming from a wide range of academic disciplines and clinical specialties.
The 2021 Research Excellence Framework (REF) confirmed the University of Bristol’s position as a leading centre for health research. Bristol Medical School contributed to three Units of Assessment including UoA1 (Clinical Medicine), UoA2 (Public Health, Health Services and Primary Care) and UoA4 (Psychology, Psychiatry and Neuroscience). The UoA2 submission, comprising predominantly Medical School staff. was ranked 3rd in the UK with 94% of our submitted research outputs rated as world leading (4*) or internationally excellent (3*). Submissions to UoA1 and UoA4 were shared with varying degrees of representation with the Faculty of Life Sciences. Respectively UoA1 and UoA4 had 94% and 84% of submitted research ranked as 4* or 3*, which represented increases in each category in the proportions of 4* ranked papers as well in growth in GPA rankings above the previous REF2014.
The Medical School has responsibility for the undergraduate medical (MBChB) programme. Undergraduate and postgraduate teaching programmes within the School provide training and career development for undergraduate and intercalating medical students, academic clinical trainees, other clinicians, and research staff. There are taught postgraduate programmes in Epidemiology, Molecular Neuroscience, Orthopaedic Research, Perfusion Science, Public Health, Reproduction and Development, Stem Cells and Regeneration, and Translational Cardiovascular Medicine. There is an active programme of research seminars in term-time.
The School is committed to delivering a positive working environment for all staff, it holds Silver Athena SWAN Awards in recognition of the ongoing commitment to promote equality, diversity and inclusion within the School.
Candidate requirements:
We strongly encourage applications from a range of disciplines (e.g., mathematics, statistics, computer science, life or natural sciences, psychology, social sciences or other related quantitative discipline). Applications are sought from high performing individuals who have, or are expected to obtain, a 2.1 or higher degree (or equivalent). Possession of a relevant Master's degree or research experience would be advantageous but is not expected.
How to apply
When applying, candidates must select the Population Health PhD programme and enter supervisor names as listed under the project title for which they are applying. Please state IEU funding in the funding box. Full details on what to include in your application can be found in the Admissions Statement.
Personal statement: Please also provide a personal statement that describes your training and experience so far, your motivation for doing a PhD, your motivations for applying to the University of Bristol, and why you think we should select you. We are keen to support applicants from minority and under-represented backgrounds (based on protected characteristics) and those who have experienced other challenges or disadvantages. We encourage you to use your personal statement to ensure we can take these factors into account.
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