Assessing causal relationships using genetic proxies for exposures: an introduction to Mendelian randomization

38Citations
Citations of this article
83Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background and aims: Studying the consequences of addictive behaviours is challenging, with understanding causal relationships from observational data being particularly difficult. For example, people who smoke or drink excessively are often systematically different from those who do not, are less likely to participate in research and may misreport their behaviours when they do. Furthermore, the direction of causation between an addictive behaviour and outcome may be unclear. Mendelian randomization (MR) offers potential solutions to these problems. Methods: We describe MR's principles and the criteria under which it is valid. We identify challenges and potential solutions in its application (illustrated using two applied examples) and describe methodological extensions in its application. Results: MR is subject to certain assumptions, and requires the availability of appropriate genetic data, large sample sizes and careful design and conduct. However, it has already been applied successfully to the addiction literature. The relationship between alcohol consumption (proxied by a variant in the ADH1B gene) and cardiovascular risk has been investigated, finding that alcohol consumption increases risk, with no evidence of a cardioprotective effect at moderate consumption levels. In addition, heaviness of smoking (proxied by a variant in the CHRNA5-A3-B4 gene cluster) and risk of depression and schizophrenia have been investigated, with no evidence of a causal effect of smoking on depression but some evidence of a causal effect on schizophrenia. Conclusions: Mendelian randomization analyses are already producing robust evidence for addiction-related practice and policy. As genetic variants associated with addictive behaviours are identified, the potential for Mendelian randomization analyses will grow. Methodological developments are also increasing its applicability.

Cite

CITATION STYLE

APA

Katikireddi, S. V., Green, M. J., Taylor, A. E., Davey Smith, G., & Munafò, M. R. (2018). Assessing causal relationships using genetic proxies for exposures: an introduction to Mendelian randomization. Addiction, 113(4), 764–774. https://doi.org/10.1111/add.14038

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free