Mendelian randomization
In epidemiology, Mendelian randomization (commonly abbreviated to MR) is a method using measured variation in genes to examine the causal effect of an exposure on an outcome.
Under key assumptions (see below), the design reduces both reverse causation and confounding, which often substantially impede or mislead the interpretation of results from epidemiological studies.
There are many epidemiological study designs that aim to understand relationships between traits within a population sample, each with shared and unique advantages and limitations in terms of providing causal evidence, with the "gold standard" being randomized controlled trials.
Some observational studies found an association between higher circulating selenium levels (usually acquired through various foods and dietary supplements ) and lower risk of prostate cancer.
[6] Mendelian randomization methods now support the view that high selenium status may not prevent cancer in the general population, and may even increase the risk of specific types.
[9] As genotypes are assigned randomly when passed from parents to offspring during meiosis, then groups of individuals defined by genetic variation associated with an exposure at a population level should be largely unrelated to the confounding factors that typically plague observational epidemiology studies.
Germline genetic variation (i.e. that which can be inherited) is also temporarily fixed at conception and not modified by the onset of any outcome or disease, precluding reverse causation.
[15] Additionally some biases that arise from violations of the second IV assumption, such as dynastic effects, can be overcome through the use of data which includes siblings or parents and their offspring.
[citation needed] Since that time the literature includes examples of research using molecular genetics to make inference about modifiable risk factors, which is the essence of MR. One example is the work of Gerry Lower and colleagues in 1979 who used the N-acetyltransferase phenotype as an anchor to draw inference about various exposures including smoking and amine dyes as risk factors for bladder cancer.
[3] In their 2003 paper, Shah Ebrahim and George Davey Smith use the term again to describe the method of using germline genetic variants for understanding causality in an instrumental variable analysis, and it is this methodology that is now widely used and to which the meaning is ascribed.
[20] The Mendelian randomization method is now widely adopted in causal epidemiology, and the number of MR studies reported in the scientific literature has grown every year since the 2003 paper.
