What can Mendelian randomization contribute to biological anthropology?

Abstract

AbstractUncovering causal relationships between exposures and outcomes can be difficult in observational studies because of the potential for confounding and reverse causation to produce biased estimates. Conversely, randomized controlled trials (RCTs) provide the strongest evidence for causality but they are not always feasible. Mendelian randomization (MR) is a method that aims to strengthen causal inference using genetic variants as proxies or instrumental variables (IVs) for exposures, to overcome the above‐mentioned biases. Since allele segregation occurs at random from parents to offspring, and alleles for a trait assort independently from those for other traits, MR studies have frequently been compared to “natural” RCTs. In biological anthropology (BA) relationships between variables of interest are usually evaluated using observational data, often remaining descriptive, and other approaches to causal inference have seldom been implemented. Here, we propose the use of MR to investigate cause and effect relationships in BA studies and provide examples to show how that can be done across areas of BA relevance, such as adaptation to the environment, nutrition and life history theory. While we consider MR a useful addition to the biological anthropologist's toolbox, we advocate the adoption of a wide range of methods, affected by different types of biases, in order to better answer the important causal questions for the discipline.