Researchers say understanding the role our genes play in multiple sclerosis risk can help us understand the disease better.
Researchers are delving deeper into the role genes may play in a person’s risk of developing multiple sclerosis (MS).
“We think the genetic contribution to risk for MS is probably about 30 percent or so,” Bruce Bebo, PhD, executive vice president of research at the National Multiple Sclerosis Society, told Healthline. “So, in the case of identical twins, if one has MS, the other gets it about 30 percent of time.”
“The rest of the risk is coming from environment exposures and (other) factors,” he noted.
Bebo said the data suggests that if “a first-degree relative has MS, then your risk is around 5 to 10 fold higher than general population’s.”
“While this sounds scary,” Bebo added, “the risk in the general population is very low.”
Researchers speculate that in the near future this information could also be used to derive personalized approaches to treatments.
Studies have shown that MS is most prevalent in individuals of northern European ancestry and carries substantial heritability. But, it takes rare variants to coexist in order to create MS.
One analysis, published in
An extensive analysis published by the International Multiple Sclerosis Genetics Consortium in Cell in 2018 reviewed 68,000 cases and identified more than 200 genetic variants associated with the risk of MS.
Using a different approach, researchers took a look at the association between genes and MS using exome sequencings. Results from 132 people with MS in 34 different families identified 12 candidate genes and suggested pathways for disease.
“This is an interesting study by a respected team that adds information to the body of evidence related to the genes that make people susceptible to developing multiple sclerosis,” explained Bebo. “Ultimately, this kind of work will contribute to efforts to understand what goes wrong in the disease and how to fix it and even prevent it.”
Dr. Jaime Imitola, FAAN, director of Multiple Sclerosis and Translational Neuroimmunology at the University of Connecticut School of Medicine talked to Healthline to help interpret all this data.
Imitola clarified the distinction in risk between familial MS and the other forms of MS, such as spontaneous.
“Familial MS is less than 15 percent of all the cases of MS, so whatever is found in research is only applicable to a minority of patients,” Imitola said.
“Every paper about genetics and MS is helpful and useful. They provide new evidence as to what may be the origin of MS,” Imitola noted.
He said MS requires genetics and immune activation. That could be an infection, but it also requires the environment to susceptibility for MS.
“MS is not just one disease with one single mechanism,” Imitola explained. “Risk factors such as watching vitamin D levels and not smoking can help prevent the origin of MS.”
“The key issue to learn is that there is genetic influences in MS, but they come in different ways,” he added.
“Genes are associated with onset, progression, repair,” said Imitola. “Possibly we will be able to find other variants.”
Imitola emphasized the importance of the information derived from the genome-wide studies because they are able to be translated into biological significance.
While studies in familial cases can illuminate pathways of gene candidates, they are not replicated and functional studies haven’t been done.
Bebo says the “exome sequencing approach” needs more confirmation. He would like to see other groups confirm these findings.
He is hopeful, however, that this approach may help define more precisely the risk of MS.
The data is not yet sufficient to be used for determining diagnosis or prognosis, Bebo said.
Revealing pathways could help target new treatments.
“We’re learning more about contribution of genetics in MS that could eventually be used to help us personalize treatment and identify new targets for better and more effective therapies,” explained Bebo. “We are not there yet. This is where we need to go.”
Bebo emphasized that using this information to help attack the disease early could be helpful.
The National Institutes of Health Clinical Center in Bethesda, Maryland, is currently recruiting for a clinical trial to evaluate a score for genetic and environmental risk factors.
The research may help predict whether a person will develop MS.
Learn more at clinicaltrials.gov.
Caroline Craven is a patient expert living with MS. Her award-winning blog is GirlwithMS.com, and she can be found on Twitter.