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Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis
journal contributionposted on 2016-12-01, 00:00 authored by C Tao, S Simpson, I van der Mei, L Blizzard, E Havrdova, D Horakova, V Shaygannejad, A Lugaresi, G Izquierdo, M Trojano, P Duquette, M Girard, F Grand'Maison, P Grammond, R Alroughani, M Terzi, C Oreja-Guevara, S A Sajedi, M Barnett, Cameron ShawCameron Shaw
BACKGROUND: Age at onset (AAO) in multiple sclerosis (MS) is an important marker of disease severity and may have prognostic significance. Understanding what factors can influence AAO may shed light on the aetiology of this complex disease, and have applications in the diagnostic process. METHODS: The study cohort of 22 162 eligible patients from 21 countries was extracted from the MSBase registry. Only patients with MS aged ≥16 years were included. To reduce heterogeneity, only centres of largely European descent were included for analysis. AAO was defined as the year of the first symptom suggestive of inflammatory central nervous system demyelination. Predictors of AAO were evaluated by linear regression. RESULTS: Compared with those living in lower latitudes (19.0-39.9°), onset of symptoms was 1.9 years earlier for those at higher latitudes (50.0-56.0°) (p=3.83×10(-23)). A reciprocal relationship was seen for ambient ultraviolet radiation (UVR), with a significantly increasing AAO for patients with MS per each quartile increment of ambient UVR (p=1.56×10(-17)). We found that the AAO of female patients was ∼5 months earlier than male patients (p=0.002). AAO of progressive-onset patients with MS were ∼9 years later than relapsing-onset patients (p=1.40×10(-265)). CONCLUSIONS: An earlier AAO in higher latitude regions was found in this worldwide European-descent cohort and correlated inversely with variation in latitudinal UVR. These results suggest that environmental factors which act at the population level may significantly influence disease severity characteristics in genetically susceptible populations.
JournalJournal of neurology, neurosurgery & psychiatry
Pagination1343 - 1349
Publication classificationC Journal article; C1.1 Refereed article in a scholarly journal
Copyright notice2017, by the BMJ Publishing Group Ltd.
AdolescentAdultAge of OnsetAustraliaCohort StudiesEuropeFemaleGenetic Predisposition to DiseaseGeneticsGeography, MedicalHumansMaleMultiple SclerosisMultiple Sclerosis, Relapsing-RemittingRisk FactorsUltraviolet RaysYoung AdultScience & TechnologyLife Sciences & BiomedicineClinical NeurologyPsychiatrySurgeryNeurosciences & NeurologyGENETIC RISK SCOREENVIRONMENTAL-FACTORSULTRAVIOLET-RADIATIONNATURAL-HISTORYSUN EXPOSUREVITAMIN-DPREVALENCEBIRTHPOPULATIONPHENOTYPEMSBase Study Group