In MS, the immune system attacks myelin, the fatty sheath that protects the cells of the central nervous system, rather like plastic insulation that protects electrical cables.
As a result, "short circuits" occur in the body's messaging system, because nerve signals get slowed or blocked. This leads to difficulties in movement and coordination, muscle weakness, cognitive impairment, slurred speech and vision problems.
Until now, investigations of the human genome have turned up only a cluster of variants of genes on Chromosome 6, in the so-called Major Histocompatibility Complex, which regulates the immune system.
But these genes were identified in the mid-1970s, leaving frustrated doctors to hunt for other culprits in the complex cascade of processes involved in MS.
The new suspects play a role in guiding key immune cells, called T cells, which patrol the body for intruders.
They carry the name of interleukin-7 receptor alpha, or IL7R-alpha, located on Chromosome 5, and interleukin-2 receptor alpha (IL2R-alpha) on Chromosome 10, which has previously been associated with Type 1 diabetes.
A single change in the genetic code in IL7-R, and two changes in IL2-R create the dangerous variants.
Each variant appears to boost the risk of MS by between 20 and 30 percent.
"Our finding is very important, because the genetic factors that are already known to be associated with multiple sclerosis only explain less than half of the total genetic basis for the disease," said Simon Gregory, a geneticist at Duke University in Durham, North Carolina, who took part in the IL7-R work.
The two studies, published simultaneously by Nature Genetics and the New England Journal of Medicine (NEJM), were carried out by two consortia of scientists, from the United States and Cambridge University, England.
The genetic variants were unearthed thanks to a comparison of more than 20,000 samples of DNA, provided by patients diagnosed with MS and those without the disease, living in the United States and Europe.
"People have been looking for genes involved in MS for 30 years," said David Hafler, a professor of neurology at Harvard Medical School, a lead author on the IL2-R study.
"Why weren't they found? The answer is, you couldn't do it without the sequence of the human genome."
Around 350,000 people in the United States have MS, and at least two-thirds of them are women, according to US figures.
The disease is most common in young adults, with more than 90 percent of cases being diagnosed before the age of 55 and fewer than five percent diagnosed before the age of five.
At present, there is no cure for the disease. But identifying genetic links throws up exciting new avenues of investigation into treatments that, ideally, would block the disease or at least slow its progression.
Other mooted causes for MS include a virus or exposure to some environmental agent.