Largest Genetics Study Ever Performed for Multiple Sclerosis Identifies Dozens of Genetic Factors that Influence MS Risk

The authors of “Analysis of Immune-Related Loci Identifies 48 New Susceptibility Variants for Multiple Sclerosis,” published in Nature Genetics, genotyped a large cohort that included patients with multiple sclerosis and healthy controls, looking at more than 160,000 autosomal variants for regions that are potentially associated with multiple sclerosis.

Specifically, they analyzed nearly 15,000 subjects (N = 14,498) with multiple sclerosis and more than 24,000 healthy controls (N = 24,091) for 161,311 autosomal variants, identifying 135 “potentially associated regions.” They added these data to “previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls.”

From this total group of more than 80,000 individuals, the researchers identified “48 new susceptibility variants,” bringing the toal of “established multiple sclerosis risk variants” to 110 at “103 discrete loci outside of the major histocompatibility complex.”

The researchers reported mapping and identifying “five regions where one variant accounted for more than 50% of the posterior probability of association.” They concluded that “this study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.”

A news release from the University of Miami Miller School of Medicine that accompanied publication of the article said that this study “provides additional key insights into the biology of this debilitating neurological condition,” and that “the genes implicated by the newly identified associations underline the central role played by the immune system in the development of multiple sclerosis and show substantial overlap with genes known to be involved in other autoimmune diseases.”

Although each genetic variant individually confers “only a very small risk of developing multiple sclerosis, collectively they explain approximately 20 percent of the genetic component of the disease.”

In the release, lead author Jacob McCauley, PhD, said the ongoing effort “to elucidate the genetic components of this complex disease has taken a major step forward. Describing the genetic underpinnings of any complex disease is a complicated but critical step. By further refining the genetic landscape of multiple sclerosis and identifying novel genetic associations, we are closer to being able to identify the cellular and molecular processes responsible for MS and therefore the specific biological targets for future drug treatment strategies. These results are the culmination of a thoroughly collaborative effort. A study of this size and impact is only possible because of the willingness of so many hard working researchers and thousands of patients to invest their time and energy in a shared goal.”