A higher burden of multiple sclerosis genetic risk confers an earlier onset. (July 2022)

• Record Type: Journal Article
• Authors: Misicka, Elina; Davis, Mary F; Kim, Woori; Brugger, Steven W; Beales, Jeremy; Loomis, Stephanie; Bronson, Paola G; Briggs, Farren BS
• Is Part Of: Multiple sclerosis. Volume 28:Number 8(2022)
• Page Start: 1189
• Page End: 1197
• Publication Date: 2022-07
• Subjects: Epidemiology -- genetics -- multiple sclerosis -- age at onset -- genetic risk score; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/13524585211053155
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: Age at onset of multiple sclerosis (MS) is an objective, influential predictor of the evolution of MS independent of disease duration. Objectives: Determine the influence of MS genetic predisposition on age of onset. Methods: We conducted a comprehensive investigation of MS risk variants and age at onset in 3495 non-Latinx white individuals, including for combinations of HLA-DRB1*15:01 alleles and quintiles of an unweighted genetic risk score (GRS) for 198 of 200 autosomal MS risk variants that reside outside the major histocompatibility complex. Results: The mean age at onset was 32 years, 29% were male, and 46% were HLA-DRB1*15:01 carriers. For those with the greatest genetic risk burden (the highest GRS quintile with two HLA-DRB1*15:01 alleles) were on average 5 years younger at onset ( p = 0.002) than those with the lowest genetic risk burden (the lowest GRS quintile with no HLA-DRB1*15:01 alleles). There was a strong inverse relationship between the MS genetic risk burden and age at onset of MS ( p < 5 × 10 −8 ). Conclusion: We demonstrate a significant gradient between elevated MS genetic risk burden and an earlier onset of MS, suggesting that a higher MS genetic risk burden accelerates onset of the disease.