MS Genomics: A Complex Code

In spring 2007, half-a-dozen scientists huddled around a laptop at a pub in Cambridge in the United Kingdom, to see the preliminary results from the largest ever genetic study of multiple sclerosis (MS). Expectations were high. Three decades had passed since the last genes were discovered to have a link to MS, in a large genomic region called the major histocompatibility complex (MHC).Using the pub's wireless Internet connection, one of the researchers eagerly downloaded the first batch of data. It was disappointing: the analysis found no gene variants outside the MHC that were associated with MS. “We thought, all this work and once again MS eludes us,” recalls David Hafler, one of the leaders of the International Multiple Sclerosis Genetics Consortium (IMSGC).The next morning, when the researchers convened again at the University of Cambridge, they were in for a pleasant surprise. “The guy who had downloaded the data said: 'Oh, I made a mistake',” recalls Hafler, who is now head of neurology at Yale University. When the analysis was done again, the program identified variants near two genes that play an important role in the workings of immune cells.

The report included data from almost 4,000 people with MS. In August 2011, the consortium published an even bigger association study. After screening the genomes of nearly 10,000 people with MS, the group found dozens of genetic variants significantly associated with the disease. An intriguing proportion of these variants fall near genes related to the immune system, bolstering the notion that MS is fundamentally an auto-immune disease that leads to brain degeneration, rather than the other way round. “This disease has an astonishingly immunological flavour,” says Alastair Compston, head of clinical neurosciences at the University of Cambridge and another founding member of the IMSGC.

The hope, Compston says, is that studying these variants will point researchers towards shared biological pathways that would make good targets for drugs.Read more at...Nature, April 2012.