WenJun Zhang School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; International Academy of Ecology and Environmental Sciences, Hong Kong, China Network Biology ISSN 2220-8879 http://www.iaees.org/publications/journals/nb/online-version.asp 2025 15 2 24 47 International Academy of Ecology and Environmental Sciences Hong Kong 8 January 2024 19 February 2024 1 June 2025 Mendelian randomization causality causal inference genetic association exposure outcome confounder Mendelian randomization (MR) is a methodology for evaluating causality in observational studies. MR tries to find the fact that genotypes are not susceptible to reverse causation and confounding based on Mendel's law of inheritance. MR may provide information on causality in situations where randomized controlled trials are impossible. In present article, the principles and methods of MR were fully discussed. http://www.iaees.org/publications/journals/nb/articles/2025-15(2)/Mendelian-randomization-Principles-and-methods.pdf