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Twins Study Points to Environmental Cause for MS

With near-identical DNA, why does one twin get the illness while the other does not?

WEDNESDAY, April 28 (HealthDay News) -- Genetics can't seem to explain why one twin would have multiple sclerosis while an identical twin doesn't, a new study finds.

That leaves scientists still stumped as to what causes multiple sclerosis (MS), although it's clearer than ever that environmental factors play a major role.

"We found that these twins had a lot of genetic risk factors for MS and yet the twins were born on the same day in the same family, grew up together, ate the same food, went to the same schools and they [both] had that predisposition, that set of risk factors. But, one developed the disease and one didn't," said study senior author Dr. Stephen Kingsmore.

"This points to some environmental trigger that protected one of the twins or triggered the disease in one of the twin members," added Kingsmore, who is CEO of the National Center for Genome Resources in Santa Fe, NM.

According to the researchers, this was the first use of a genome-wide analysis to study an autoimmune disease in identical twins.

The findings are published in the April 29 issue of Nature.

Little is known about the causes of MS, an autoimmune disorder in which the body attacks the myelin sheath that protects the nerve fibers of the central nervous system. It can cause vision problems, muscle weakness, and thinking and memory difficulties.

Genes -- not one, but many -- clearly play some kind of role, as do as-yet-unidentified environmental factors.

One mystery surrounding the disease has been why 30 to 40 percent of identical twin pairs develop MS, while the rest don't.

"What makes up the other 60 or 70 percent?" asked Patricia O'Looney, vice president of biomedical research at the National Multiple Sclerosis Society in New York City.

The researchers set out to see if genetic differences accounted for the discrepancy, given that it's now known that not all identical twins are 100 percent identical.

"A couple of studies in recent years have suggested that identical twins are not identical," Kingsmore said. "We were kind of betting on the fact that [the twins in this study] wouldn't be identical."

Kingsmore and his colleagues looked at three pairs of identical twins in which one twin had MS and the other did not. The oldest twins were in their 50s, the youngest 19.

Three different genetic analyses allowed them to look not only at the genes the twins were born with, but also at gene expression and what's known as imprinting or epigenetics -- when genes change their activity over the course of a lifetime.

"It gives us a very good description of a genome that's not static," Kingsmore said. "We weren't just looking at what you were born with."

Still, the authors failed to find any genetic explanation for the discrepancy between the twins.

"At the end of the day, we looked under a rock and found no genetic differences in these three pairs of twins," Kingsmore said. "It was quite a surprise."

The authors feel they may have ruled out some genetic causes for the disease but, other than that, what triggers MS is still an unanswered question.

The group plans further genetic studies to see if anything was missed the first time around.

"We still don't have the answers, that's for sure, but this was only three pairs of twins," O'Looney pointed out. "Further work needs to take place."

"It's a big mystery," added Kingsmore. "There's an unknown or undiscovered environmental trigger that's really important."

More information

There's more on MS at the National Multiple Sclerosis Society.

SOURCES: Stephen Kingsmore, M.B, Ch.B, president and chief executive officer, National Center for Genome Resources, Santa Fe, NM; Patricia O'Looney, Ph.D., vice president of biomedical research, National Multiple Sclerosis Society, New York City; April 29, 2010 Nature

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