Using Mendelian randomization to understand and develop treatments for neurodegenerative disease

Abstract

Common neurodegenerative diseases are thought to arise from a combination of environmental and genetic exposures. Mendelian randomization is a powerful way to leverage existing genetic data to investigate causal relationships between risk factors and disease. In recent years, Mendelian randomization has gathered considerable traction in neurodegenerative disease research, providing valuable insights into the aetiology of these conditions. This review aims to evaluate the impact of Mendelian randomization studies on translational medicine for neurodegenerative diseases, highlighting the advances made and challenges faced. We will first describe the fundamental principles and limitations of Mendelian randomization and then discuss the lessons from Mendelian randomization studies of environmental risk factors for neurodegeneration. We will illustrate how Mendelian randomization projects have used novel resources to study molecular pathways of neurodegenerative disease and discuss the emerging role of Mendelian randomization in drug development. Finally, we will conclude with our view of the future of Mendelian randomization in these conditions, underscoring unanswered questions in this field.