International Journal of Epidemiology, Volume 33, Number 1, pp. 21-25
IJE vol.33 no.1 © International Epidemiological Association 2004; all rights reserved.
Reprints and Reflections |
Commentary: The concept of ‘Mendelian Randomization’
Department of Preventive Medicine, University of Southern California, Los Angeles, CA 9089-9011, USA
| The first 150 words of the full text of this article appear below. |
This issue of the International Journal of Epidemiology reprints a seminal letter to the editor by Martijn Katan,1 which appears to be the first description of the concept of ‘Mendelian randomization.’ In discussing the controversy over whether the association between low serum cholesterol and cancer is causal or might simply reflect an effect of the disease to lower cholesterol levels (‘reverse causation’) or confounding by diet or other factors, Katan proposed a test of causality by studying instead the relationship between cancer and a genetic determinant of serum cholesterol, the apolipoprotein A (APOE) gene. His rationale was that since alleles are allocated essentially at random, such an association would not be subject to either confounding or reverse causation. Thus, if a causal relationship between APOE and serum cholesterol were clearly established, then an association between APOE and cancer would provide indirect evidence for the causality of the association
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Use of instrumental variables in epidemiology |
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Complications |
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Direct effect of G on D not mediated through IP
Gene—environment interactions
Gene—gene interactions
Population stratification
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Conclusions |
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Appendix |
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Validity and efficiency of the ‘instrumental variables’ approach
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