Latest scientific news 06 January 2020

Critical review of Mendelian randomisation used in research of alcoholic beverages

This critical review proposes to regard Mendelian RandomizationThe basic idea of the Mendelian randomization is to use genetic variables as instrumental variables ... (MR) as another type of observational study, not as an alternative to observational studies to determine causality. The researchers highlight the limitations of MR when applied to the associations of alcohol consumption with cardiovascular disease (1).

MR is a method that is increasingly being used to conduct studies on alcoholic beverages and health and as result challenges the findings of previous research, such as the J-shaped curve.

What does it mean:

This paper (1) is a critical analysis of the MR method used in recent research on alcoholic beverages that has generated debate in the scientific community and the public. Some researchers have claimed that the results of certain MR studies (2,3) disprove the protective effect of moderate drinking for cardiovascular disease (CVD). The authors of the current publication argue that – because of a number of limitations – MR should be viewed as another type of observational study and therefore, should not be seen to negate the existing body of evidence which supports the J-curve relationship between drinking and CVD.


  1. Mukamal, K. J., Stampfer, M. J., & Rimm, E. B. (2019). Genetic instrumental variable analysis: Time to call Mendelian randomization what it is. The example of alcohol and cardiovascular disease. European Journal of Epidemiology. doi:10.1007/s10654-019-00578-3.
  2. Holmes, M. V., Dale, C. E., Zuccolo, L., Silverwood, R. J., Guo, Y., & Engmann, J. (2014). Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. British Medical Journal, 349
  3. Millwood, I. Y., Walters, R. G., Mei, X. W., Guo, Y., Yang, L., Bian, Z., et al. (2019). Conventional and genetic evidence on alcohol and vascular disease aetiology: A prospective study of 500,000 men and women in China. The Lancet, 393, 1831-1842.

Mendelian RandomizationThe basic idea of the Mendelian randomization is to use genetic variables as instrumental variables ... (MR) – Background information:

In recent years, epidemiologists have increasingly sought to use genetic data to find “causal” relationships between the exposures of interest and various endpoints, for example exposure to alcoholic beverages and cardiovascular disease as endpoint. This approach is called Mendelian randomization (MR).

The problem in observational studies is establishing causality. A best way to test cause and effect associations are long-term clinical trials, however, long-term trials on diet or drinking patterns, are not readily tested in randomized trials.

What is Mendelian randomization?


Fig. 1

MR is a research method that uses an individual’s genes to estimate their behavior, rather than asking them to report their behavior. Genes vary across a population and these variations can influence behavior (known as a ‘genetic proxy’ for the behavior). In MR, researchers use these genetic proxies to see, if certain behaviors are linked to health outcomes, such as specific diseases.

Why is MR used?

MR can be used as an alternative to a traditional method of analyzing the consumption of alcoholic beverages (epidemiology) [1, 2], which has previously identified a J-shaped relationship between alcohol intake and cardiovascular disease (CVD). The J-curve shows that moderate drinking is associated with a lower risk of CVD compared to non-drinking or heavy drinking. But because of the nature of these epidemiological studies, this evidence on its own cannot show that the relationship is causal, and it may be that moderate drinkers are healthier than non-drinkers. Therefore, MR has been promoted as an alternative method to identify, if the link is causal or not. When used correctly, MR can remove the influence of other factors and identify direct causation between a behavior and a health outcome.

How is it used to address alcohol and health questions?

MR studies