After More Than a Generation, MS Gene Found!

AFTER A DECADES-LONG SEARCH, SCIENTISTS IDENTIFY NEW GENETIC RISK FACTORS FOR MULTIPLE SCLEROSIS

A pair of large-scale genetic studies supported by the National Institutes of Health has revealed two genes that influence the risk of getting multiple sclerosis (MS) -- data sought since the discovery of the only other known MS susceptibility gene decades ago. The findings could shed new light on what causes MS -- a puzzling mix of genes, environment and immunity -- and on potential treatments for at least 350,000 Americans who have the disease.

"These studies describe the first genes conclusively linked to MS in more than 20 years," said Ursula Utz, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH. "This breakthrough was made possible through persistence, an elegant search strategy, and genomic data and techniques that were not available until recently."

Both studies involved scanning DNA samples from more than 20,000 MS patients and unaffected individuals in the U.S. and Europe, and looking for single nucleotide polymorphisms (SNPs), which are single-letter variations in a gene's DNA code. Published simultaneously today in the "New England Journal of Medicine" and "Nature Genetics," the studies demonstrate an association between MS and SNPs in two genes that encode interleukin receptors, proteins that serve as antennae on the surface of immune cells.

Both studies were supported by NINDS and the National Multiple Sclerosis Society. The "Nature Genetics" study received additional support from the National Institute of General Medical Sciences (NIGMS). The "NEJM" study was also supported by the National Institute of Allergy and Infectious Diseases (NIAID), the National Center for Research Resources (NCRR) and the Penates Foundation.

They were conducted by overlapping teams of scientists that used different gene-hunting strategies. One team, which scanned the entire human genome for MS risk factors, was co-led by David Hafler, M.D., Professor of Neurology at Harvard Medical School and Brigham and Women's Hospital in Boston, Stephen Hauser, M.D., Professor and Chair of Neurology at the University of California in San Francisco, and Alastair Compston, FRCP, Ph.D., Head of the Department of Clinical Neurosciences at the University of Cambridge, U.K. The other team, which focused their search on a set of genes they considered potential risk factors for MS, was co-led by Jonathan Haines, Ph.D., Director of the Center for Human Genetics Research at Vanderbilt University Medical Center in Nashville, Tenn. and Margaret A. Pericak-Vance, Ph.D., Director of the Miami Institute for Human Genomics at the University of Miami. Drs. Hauser, Compston, Haines and Pericak-Vance participated in both studies.