Mendelian randomization in multiple sclerosis: A causal role for vitamin D and obesity?
Adil Harroud, J Brent Richards
Author Information
Adil Harroud: Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada/Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.
J Brent Richards: Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada/Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada/Department of Human Genetics, McGill University, Montreal, QC, Canada/Department of Medicine, McGill University, Montreal, QC, Canada/Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
The etiology of multiple sclerosis (MS) involves a complex interplay of genetic and environmental factors. Epidemiologic studies have furthered our understanding of these risk factors but remain limited by residual confounding and potential for reverse causation, particularly in MS where time of disease onset is not known. Mendelian randomization (MR) uses genetic variants to study the causal effect of modifiable exposures on an outcome. This method avoids some of the limitations of classical epidemiology and can strengthen causal inference. Here, we introduce the basic concepts of MR and review its contributions to the field of MS. Indeed, several studies using MR have now provided support for a causal role for low vitamin D level and obesity in the development of MS.
