How has Multiple Sclerosis Prevalence Evolved?

Summary

Multiple sclerosis (MS) is a genetic disease with a complex risk profile. In addition, it is more common in populations of European ancestry, and more common further from the equator within those populations. It is likely that this pattern has been shaped by natural selection. Identifying genes that have undergone selection and are implicated in MS risk will improve understanding of what causes the disease. This project is designed to identify specific combinations of genetic variants that cause MS and have undergone natural selection and help to understand the mechanisms of disease. 

This study will carry out genome-wide scans for natural selection and target regions of the genome known to be associated with MS risk. This will generate knowledge regarding the selective forces that have driven the differences in MS risk between populations, enabling more informed targeting of the molecular mechanisms behind the disease. 

Dr Bennet McComish and his team will examine the evolutionary causes of the strong latitude gradient in MS prevalence that is observed in some populations. Identifying specific genes that are under local selection in response to environmental factors will help to better target therapies aimed at these risk factors. 

They will test whether specific combinations of genetic variants that have undergone selection are associated with MS, giving us a more detailed picture of the genetic architecture that contributes to risk than we can see by considering variants one by one. Data from various parts of cell biology will be investigated to confirm the importance of any genes identified.