PT  - JOURNAL ARTICLE
AU  - Anna Karin Hedström
AU  - Jan Hillert
AU  - Tomas Olsson
AU  - Lars Alfredsson
TI  - Factors affecting the risk of relapsing-onset and progressive-onset multiple sclerosis
AID  - 10.1136/jnnp-2020-325688
DP  - 2021 Oct 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 1096--1102
VI  - 92
IP  - 10
4099  - http://jnnp.bmj.com/content/92/10/1096.short
4100  - http://jnnp.bmj.com/content/92/10/1096.full
SO  - J Neurol Neurosurg Psychiatry2021 Oct 01; 92
AB  - Objective It has been debated whether the different clinical disease courses in multiple sclerosis (MS) are the consequence of different pathogenic mechanisms, with distinct risk factors, or if all MS clinical phenotypes are variations of similar underlying disease mechanisms. We aimed to study environmental risk factors and their interactions with human leucocyte antigen DRB1*15:01 with regards to relapsing-onset and progressive-onset MS.Methods We used two Swedish population-based case–control studies, including 7520 relapsing-onset cases, 540 progressive-onset cases and 11 386 controls matched by age, sex and residential area. Logistic regression was used to estimate ORs with 95% CIs for associations between the different MS phenotypes and a number of environmental and lifestyle factors. Interaction between the DRB1*15:01 allele and environmental risk factors was evaluated on the additive scale.Results All environmental and lifestyle factors associated with risk of developing MS apply to both relapsing-onset and progressive-onset disease. Smoking, obesity and Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibody levels were associated with increased risk of both MS phenotypes, whereas snuff use, alcohol consumption and sun exposure were associated with reduced risk. Additive interactions between DRB1*15:01 and smoking, obesity, EBNA-1 antibody levels and sun exposure, respectively, occurred to increase MS risk regardless of the clinical phenotype.Interpretation Our finding that the same environmental and lifestyle factors affect both relapsing-onset and progressive-onset MS supports the notion that the different clinical phenotypes share common underlying disease mechanisms.Data are available upon reasonable request. Anonymised data will be shared by request from any qualified investigator that wants to analyse questions that are related to the published article.