News : 2018 : November

Spotlighting Advancements in MS Research

This autumn brought news of some major advancements in Multiple Sclerosis (MS) research.
Efforts by Dr. Jacob L. McCauley, Associate Professor in the Dr. John T. Macdonald Foundation Department of Human Genetics who also serves as Director of the Center for Genome Technology and Biorepository Facility at the John P. Hussman Institute for Human Genomics, and colleagues recently identified four new genes that contribute to MS risk and, in a separate study, revealed that people with Native American ancestry are significantly more likely to have optic neuritis as a first symptom of MS.
“I’m very excited about both these studies,” said Dr. McCauley. “Pinpointing the causes and initial symptoms of MS has real-world applications in that doing so can, down the road, guide other researchers in the development of therapeutic targets and allow for earlier diagnoses in clinical settings.”
Previous work by the International Multiple Sclerosis Genetics Consortium (IMSGC), of which Dr. McCauley is a member, has identified 233 genetic risk variants for MS. All together, these 233 genetic risk variants only account for about 20 percent of overall disease risk. The IMSGC knew there must be more genes. To find them, IMSGC members pooled more than 68,000 MS patients and control subjects from Australia, ten European countries, and the United States to look for rare variants that damage the gene sequence directly. They found four new genes, each of which acts independently as a risk factor for this disabling autoimmune disorder, which they report in the journal Cell.
“The four genes we discovered explain another 5% of MS risk,” said Dr. McCauley. “Using a much larger sample size than previous studies was what made the search for rare genetic variants possible.”
Accounting for 25% of the risk for developing MS is a major breakthrough. The 233 genetic risk variants mentioned earlier explain about 0.09% each, on average. The newly discovered genes explain about 1.25% of MS risk each, on average, which makes them better predictors.
To achieve the other research breakthrough, Dr. McCauley and colleagues obtained data from 1,033 self-identified Hispanic/Latino individuals with MS from an ongoing study by the University of Southern California, University of Miami, University of California San Francisco, and San Juan MS Center. The team analyzed information on genetic ancestry (examining DNA to determine ancestry), age at MS onset, and the occurrence of optic neuritis (inflammation of the optic nerve) to uncover relationships among these variables.
“Our findings showed that people with Native American ancestry are more likely to have optic neuritis as a first symptom of MS,” said Dr. McCauley. “They also tend to be younger when MS first presents.”
Optic neuritis can result in blurring or graying of vision, or blindness in one eye. A dark spot in one’s field of vision called a “scotoma” can occur.
It may behoove clinicians to pay closer attention to visual symptoms that hint at MS if they practice in the southwestern United States, where Native American ancestry is common among Hispanics/Latinos.
The study, which was published in the Annals of Clinical and Translational Neurology, suggests that genetics can, in part, underlie clinical differences in people of different ethnic backgrounds.
“We will continue to explore these differences as we attempt to explain how and why MS occurs,” said Dr. McCauley. “If we could answer these questions more fully, we could set pharmaceutical researchers on the right path.”

Links to the journal articles:
Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk
Copy and paste for this journal:
https://www.cell.com/cell/fulltext/S0092-8674(18)31261-3
Native ancestry is associated with optic neuritis and age of onset in Hispanics with multiple sclerosis