Mendelian randomization applied to migraine research: Opportunities and challenges

Observational studies have linked migraine to a wide range of risk factors and diseases, although the causality of these associations is uncertain. Mendelian randomization (MR) is an analytic paradigm that exploits germline genetic variants as natural experiments, providing a framework for causal inference from observational data. In this narrative review, we summarize the core principles and assumptions of MR and highlight methodological considerations unique to its application to migraine research. We review key MR findings across several domains of migraine research, noting areas of consistent evidence, as well as conflicting results. We then discuss limitations of MR in the context of migraine research, emphasizing that MR is not a panacea for causal inference. We conclude by underscoring the need for interdisciplinary collaboration between methodologists and domain experts to prioritize patient-relevant questions, refine analytic approaches and translate genetic insights into more effective therapies.