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ECTRIMS 2022 | Genetic analysis of MS severity identifies a novel locus

Adil Harroud, MD, McGill University, Montreal, Canada, shares the results of a genetic analysis looking to understand whether there are genetic contributions to multiple sclerosis (MS) severity. A genome-wide association of age-related MS severity (ARMSS) was performed in 15,000 MS cases with long-term outcomes. Identified variants were replicated in a second cohort of 9.800 MS cases. The rs10191329 in the DYSF-ZNF638 locus was identified as the first genome-wide significant and replicated genetic modifier of MS severity. The risk allele was associated with a shorter median time to EDSS 6.0, and faster confirmed disability worsening. This variant was also found to be associated with MS pathology, and it almost doubled the cortical pathology in specific regions of the brain. Additionally, in contrast to MS susceptibility, genes likely to contribute to MS severity resided exclusively in the central nervous system. This interview took place at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress 2022 in Amsterdam, The Netherlands.

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