Summary
A method that uses genetic variants as natural experiments to infer causal effects of exposures.
In depth
Genetic variants are randomly allocated at conception, like a natural randomised trial, so they can be used as instruments to test whether an exposure causes an outcome without confounding. Assumptions: the variant affects the outcome only through the exposure.
MR uses genetic variants associated with an exposure as instruments. Three assumptions must hold: the variant is related to the exposure, is unrelated to confounders, and affects the outcome only through the exposure. Violations such as pleiotropy are checked with methods such as MR-Egger and weighted median.
A famous use showed that lifelong higher LDL cholesterol from genetic variants raises heart disease risk, supporting causal roles, whereas variants raising HDL did not protect, explaining the failure of some HDL-raising drugs. Studies of alcohol, body mass index and smoking have also used MR.
Frequently asked questions
What is Mendelian Randomisation?
A method that uses genetic variants as natural experiments to infer causal effects of exposures.
Which area of biology covers Mendelian Randomisation, and how advanced is it?
Mendelian Randomisation is one of the 54 topics in Genetics. It is rated Advanced, so it suits learners who want specialist depth. Related topics in this area include Polygenic Inheritance, Genome-Wide Association Studies, Genetic Counselling.
Why does Mendelian Randomisation matter?
MR can reduce confounding and reverse causation seen in observational studies, and helps prioritise drug targets.
Can you give an example of Mendelian Randomisation?
Variants raising LDL cholesterol are associated with heart disease, supporting that LDL is causal.
What should I learn before Mendelian Randomisation?
Work through the Beginner topics in Genetics first, such as Heredity, Gene, Allele, then return to Mendelian Randomisation. Advanced topics assume the Intermediate vocabulary.
What topics are related to Mendelian Randomisation?
The closest topics to Mendelian Randomisation are Polygenic Inheritance, Genome-Wide Association Studies, Genetic Counselling, Epigenetics. Comparing them side by side is a good way to see how the ideas connect.
How can I check that I understand Mendelian Randomisation?
Read the summary and the in-depth section, then use the quick check on the interactive lesson for Mendelian Randomisation. To practise the whole of Genetics, use the Genetics quiz.
How is Mendelian Randomisation different from Polygenic Inheritance?
Mendelian Randomisation: A method that uses genetic variants as natural experiments to infer causal effects of exposures. Polygenic Inheritance: A trait controlled by many genes producing continuous variation, such as height and skin colour. Read both side by side and note what each one explains.
How should I study Mendelian Randomisation step by step?
First, read the summary and write the definition in your own words. Second, read the in-depth section and note any example. Third, compare it with Polygenic Inheritance and explain the difference aloud. Finally, take the Genetics quiz and come back to this page for any question you miss.