Study of twins shows no genetic cause for MS

From the San Francisco Chronicle:

The most detailed genomic analysis ever of a person with multiple sclerosis and a healthy identical twin failed to find a genetic cause for the disabling illness.

But it nonetheless underscores the exciting potential for demystifying disease through DNA, researchers said.

The study led by a UCSF neurologist took nine months to complete using some of the most advanced analysis equipment in the world, at a laboratory in Santa Fe, N.M. The results are published in today's issue of Nature.

Researcher Sergio Baranzini and his team couldn't find a genetic trigger in the twin with multiple sclerosis, but that doesn't mean it isn't there, he said. Geneticists may just need to dig deeper, with even more advanced technology, or they may need to narrow their search.

Or, it's possible that at least with this one pair of twins, genes weren't what separated them — environmental factors may have caused one sibling to develop MS, Baranzini said.

"We did not find any genetic evidence that could explain why one individual developed a disease and not the other. In that regard, it's a significant finding because no one has looked at this level of resolution before,"he said. "But I'm not surprised we didn't find it. We may be looking for one cell in a million."

The study isn't just the first to fully analyze the genomes of a pair of twins, one of whom has MS, but it's the first detailed genomic analysis of any pair of twins — period. It is also the first to analyze someone with an autoimmune disease.

Multiple sclerosis is an autoimmune disorder in which the body attacks the fatty sheaths that insulate nerves. Early symptoms can include, among other things, tingling, weakened vision, fatigue or loss of balance. After that, the disease can be unpredictable, with some people able to retain a highly functioning lifestyle while others become disabled.

Scientists don't know what causes MS, but there is almost definitely a genetic component — siblings of someone with MS have a 5 percent increased risk of developing the disease, and identical twins have a 30 percent higher risk.

Research also has pointed to possible environmental causes, including childhood viral infections or exposure to sunlight or smoking. Scientists in the genomic study didn't look at specific environmental factors.

Studying identical twins is potentially useful for finding genetic causes of diseases — if only one twin is sick, any genetic differences might leap out as possible culprits. In the case of multiple sclerosis, it's possible that, if a gene is to blame, current genomic analysis technology just isn't refined enough to find it yet.

The MS study is limited by the fact that it only fully analyzed one set of twins. And scientists who didn't participate in the study said that while the analysis is praiseworthy, it may have been too broad to catch what is likely a "needle in the haystack"genetic cause of a very complicated disease.

"This is really elegant work, and even though it's a negative, it shows the incredible depth that one can explore the issue with today's technology,"said Stanford neurologist Lawrence Steinman, a longtime multiple sclerosis researcher. "It emphasizes the fact that we haven't really identified the smoking gun, so to speak. It still drives us to want to look harder."