A higher burden of multiple sclerosis genetic risk confers an earlier onset.
Mult Scler
; 28(8): 1189-1197, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-34709090
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*1501 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*1501 carriers. For those with the greatest genetic risk burden (the highest GRS quintile with two HLA-DRB1*1501 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*1501 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esclerose Múltipla
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article