Researchers looking for rare genetic risk variants that directly damage gene sequence said they found four new genes that act independently as risk factors for multiple sclerosis. The novel variants identified code for proteins, making them easier to study, offer researchers promising new ways to study MS, the study’s authors said.

Previous work by the International Multiple Sclerosis Genetics Consortium identified 233 genetic risk variants. However, these only account for about 20 percent of overall disease risk, with the remaining genetic culprits proving elusive. To find them, the IMSGC pooled more than 68,000 MS patients and control subjects from Australia, ten European countries, and the United States. The researchers said they would not have found them by continuing to look at common genetic variants. They looked for rarer events, which means looking at many, many more people. These variants explain an extra 5 percent of risk.

Previous theories have held that combinations of common variants act in concert to explain more risk than each one alone, or that some families carry private mutations that cause disease only in those individuals. The researchers looked at thousands of people to test those theories, and said the data don’t bear them out.

The findings were published in the journal Cell.