Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology

2007/09/20 by Debbie A. Lawlor, Roger M. Harbord, Roger Harbord +5 · 22 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Folate and B Vitamins Research #Genetic Associations and Epidemiology #Nutrition, Genetics, and Disease

paper · doi:10.1002/sim.3034

openalex publication_date 2007/09/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

Observational epidemiological studies suffer from many potential biases, from confounding and from reverse causation, and this limits their ability to robustly identify causal associations. Several high-profile situations exist in which randomized controlled trials of precisely the same intervention that has been examined in observational studies have produced markedly different findings. In other observational sciences, the use of instrumental variable (IV) approaches has been one approach to strengthening causal inferences in non-experimental situations. The use of germline genetic variants that proxy for environmentally modifiable exposures as instruments for these exposures is one form of IV 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 randomized controlled trials. This paper outlines Mendelian randomization, draws parallels with IV methods, provides examples of implementation of the approach and discusses limitations of the approach and some methods for dealing with these.

Citations

• Robust, Accurate Confidence Intervals with a Weak Instrument: Quarter of Birth and Education
• Instrumental Variables Regression with Weak Instruments

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