Mendelian Randomization
• Debbie Lawlor
Professor of Epidemiology
Department of Social Medicine, University of Bristol, Bristol, United Kingdom

How Good Are Genetic Variants as Instruments for Modifiable Risk Factors?

Observational epidemiological studies suffer from many potential biases, from confounding and from reverse causation, and this limits their ability to robustly identify causal associations. In other observational sciences, notably econometrics, the use of instrumental variable approaches has been one approach to strengthening causal inferences in non-experimental situations. The use of germline genetic variants as instruments for modifiable (non-genetic) risk factors is one form of instrumental variables analysis that can be implemented within observational epidemiological studies. The method has been referred to as “Mendelian randomization”, and can be considered as analogous to randomised controlled trials. This presentation will define Mendelian randomization and instrumental variable analysis; demonstrate how the instrumental variable approach differs from multivariable regression (the more common approach to dealing with confounding in observational analysis) and discuss the potential and limitations of genetic variants as instrumental variables.

Professor Debbie A Lawlor completed medical training (University of Bristol) in 1986. She has an MPH (with distinction) from the University of Leeds, an MSc in Medical Statistics from the London School of Hygiene and Tropical Medicine and a PhD (MRC Training Fellowship, University of Bristol) in epidemiology. She is the Deputy Director of the MRC Centre for Causal Analyses in Translational Epidemiology, the scientific lead for the mother’s study in the Avon Longitudinal Study of Parent’s and Children, a UK birth cohort which began in 1991, and a co-investigator/collaborator on a number of other cohorts including the British Women’s Heart and Health Study, the Aberdeen Children of the 1950s cohort, Born in Bradford, Australian Mater University Study of Pregnancy and Raine birth cohorts, and the European Youth Hearth Health Study. Professor Lawlor has published over 250 peer-reviewed academic papers and is currently PI on over £5million grant funds. Her research is underpinned by her interest in understanding how biological (including genetic), social and environmental exposures from across the life course affect the risk of obesity, insulin resistance, diabetes, cardiovascular disease and women’s reproductive health.