Mendelian Randomization
• Shah Ebrahim
Professor of Public Health
Department of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom

Observational epidemiological studies are powerful means of understanding causal mechanisms and have successfully defined the causes of many diseases. However, examples of failures of associations demonstrated in observational epidemiology to replicate in randomized trials has caused speculation about the validity of the epidemiology approach. Underlying these failures is a lack of appreciation of the complexity of confounding, particularly by socio-economic position, and of the likelihood of reverse causation – levels of putative environmental exposures raised by sub-clinical disease – which limit causal inferences. Mendelian randomization provides a means of overcoming these problems by using genetic variants affecting proposed causal pathways as proxies for the environmental exposures. Genetic variants are inherited independently of socio-economic and other potential confounding factors and cannot be affected by reverse causality. Comparisons of disease risk by genetic variant can provide evidence for or against a causal interpretation of environmental exposures.

Essential reading: Davey Smith G, Ebrahim S. What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ May 2005; 330: 1076 – 1079

Job Title: Professor of Public Health, London School of Hygiene & Tropical Medicine

Main qualifications: DM, FRCP, FFPH

Research interests:  My main interests are in cardiovascular epidemiology, particularly in low and middle income countries, genetic epidemiology, and causes and prevention of disability in old age. I run the British Women’s Heart & Health Study, a national cohort of older women and also coordinate the Cochrane Heart Group that produces systematic reviews of the effects of interventions for heart diseases. I run the Indian migration study based in Lucknow, Hyderabad, Nagpur and Bangalore, examining the effects of migration on obesity and diabetes. I am a non-executive board member for the National Institute for Clinical & Public Health Excellence and chair the Wellcome Trust Populations & Public Health funding committee.