At the American Society of Human Genetics (ASHG) 2016 Annual Meeting in Vancouver, B.C., researchers from Harvard Medical School, the Broad Institute, and Brigham and Women's Hospital (BWH) presented data of a large-scale, genome-wide analysis of more than 110,000 samples. The researchers reported that the data, which had been collected by the International Multiple Sclerosis Genetics Consortium (IMSGC), had led to the identification of 200 genetic loci associated with multiple sclerosis (MS). This finding was explained in the presentation entitled “200 loci complete the genetic puzzle of multiple sclerosis.”
Established in 2003, the IMSGC brings together researchers from 30 institutions in 18 countries that study the genetics of MS. Through the combinations of data from multiple genome-wide association studies, the consortium was able to assemble genomic data from 47,351 individuals diagnosed with MS and 68,284 healthy controls.
"This is the largest study of this disease worldwide," explained presenter Nikolaos A. Patsopoulos, M.D., Ph.D., principal investigator in the Ann Romney Center for Neurologic Diseases at BWH, assistant professor of neurology at Harvard Medical School, and an associate member at the Broad Institute. "The large sample size provided the statistical power to pinpoint areas of the genome that are likely to be involved in MS, including less common genetic variants that tend to have a larger effect on disease."
The researchers compared the genomes of individuals with and without MS, identifying 200 variants that were significantly more widespread among those with the disease. A majority of these variants implicate genes that are associated with immune cells and immune system function, including a few potentially specific to brain-related functions.
"This confirms the complex interplay of different elements of the immune system in MS susceptibility and highlights the role of several different immune cells that contribute to the initiation of this inflammatory disease," noted senior study investigator Phil De Jager, M.D., Ph.D., director of the program in translational neuropsychiatric genomics at BWH, associate professor of neurology at Harvard Medical School, and an associate member at the Broad Institute. "While we now have some hints, the mechanisms that lead this inflammatory disease to target the brain and spinal cord remain unclear."
Remarkably, many of the genes identified were also known to be involved in other autoimmune diseases, such as rheumatoid arthritis, type I diabetes, and ulcerative colitis—raising intriguing questions about why these diseases target different organs and have different clinical manifestations.
"The differences and commonalities between MS and other autoimmune diseases are part of our line of research," Dr. Patsopoulos concluded. "Many of these conditions affect immune system cells, but we believe they change these cells in different ways, leading to different disease outcomes."