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Mendelian randomization analyses of kidney function and effects on health and mediating outcomes.

  • 8 September 2025 to 2 December 2025
  • Project No: D26030
  • DPhil Project 2026
  • Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU)

Background

Kidney disease is estimated to affect ~10% of the world’s population and causes significant burdens of death and disability through progression to kidney failure and effects on the cardiovascular and endocrinological systems. Other commonly associated but less well-understood complications include an increased risk of infections, acute kidney injury, cancer, and cognitive impairment, including dementia. 

Both traditional observational studies and genetic epidemiological analyses have shown that decreased (<90mL/min/1.73m2) estimated glomerular filtration rate (eGFR) is causally associated with increased death rates, largely driven by atherosclerotic cardiovascular disease. However, it remains unclear whether decreased eGFR is causally linked to non-atherosclerotic cardiovascular disease or to other non-cardiovascular outcomes. 

Mendelian randomization (MR), a method that uses genetic variants as instrumental variables to infer causal relationships between exposures and outcomes, largely overcomes the limitations of observational epidemiological analyses that hinder causal inference. 

The UK biobank (UKBB) is a world-leading resource of 500 000 middle-aged participants from across Great Britain, with a wealth of healthcare, imaging, metabolomic, proteomic, and genetic data, including validated genetic risk scores for eGFR.1,2 

research experience, research methods and skills training

This project will aim to investigate the causal effects of decreased kidney function on a range of conditions including cardiovascular disease (in particular, of non-atherosclerotic causes), acute kidney injury, infections, cancer, and dementia. While there is some flexibility in the scope, it is likely the project will leverage UKBB data on:

  • Routinely-collected incident health outcomes
  • Imaging outcomes including bone density, carotid plaque thickness, cardiac MRI, and brain MRI
  • Blood-based biomarkers

A range of Mendelian Randomization techniques will be employed to assess the strength and shape of the relationships, and to test important assumptions. The project will also offer opportunities to explore potential biological pathways underlying observed associations by leveraging UKBB’s metabolomics and proteomics data.

The student will develop strong skills in: epidemiological research and methodology, systematic reviews, statistical programming and data analysis, and scientific writing and communication. They will be supported in presenting their work at national and international conferences and in publishing peer-reviewed articles based on their DPhil research.

References:

FIELD WORK, SECONDMENTS, INDUSTRY PLACEMENTS AND TRAINING

The project will be based within the global studies group and renal studies group at the Big Data Institute, a world-class community for population health research where the UKB outcome derivation work has been coordinated. In-house training in statistical and epidemiological methods, programming, and scientific writing will be provided. Funding is available for external courses. 

PROSPECTIVE STUDENT

The ideal candidate will have an MSc in epidemiology, statistics, biomedical sciences or a related subject, and will have proficiency with programing analyses in R, SAS, or Python. Familiarity with Mendelian randomization methodology and with cloud-based computing (e.g., UKBB’s Research Analysis Platform) would be an advantage.  

research group