PT  - JOURNAL ARTICLE
AU  - Tao, Chunrong
AU  - Simpson, Steve
AU  - van der Mei, Ingrid
AU  - Blizzard, Leigh
AU  - Havrdova, Eva
AU  - Horakova, Dana
AU  - Shaygannejad, Vahid
AU  - Lugaresi, Alessandra
AU  - Izquierdo, Guillermo
AU  - Trojano, Maria
AU  - Duquette, Pierre
AU  - Girard, Marc
AU  - Grand'Maison, Franois
AU  - Grammond, Pierre
AU  - Alroughani, Raed
AU  - Terzi, Murat
AU  - Oreja-Guevara, Celia
AU  - Sajedi, Seyed Aidin
AU  - Iuliano, Gerardo
AU  - Sola, Patrizia
AU  - Lechner-Scott, Jeannette
AU  - Pesch, Vincent Van
AU  - Pucci, Eugenio
AU  - Bergamaschi, Roberto
AU  - Barnett, Michael
AU  - Ramo, Cristina
AU  - Singhal, Bhim
AU  - LA Spitaleri, Daniele
AU  - Slee, Mark
AU  - Verheul, Freek
AU  - Fernández Bolaños, Ricardo
AU  - Amato, Maria Pia
AU  - Cristiano, Edgardo
AU  - Granella, Franco
AU  - Hodgkinson, Suzanne
AU  - Fiol, Marcela
AU  - Gray, Orla
AU  - McCombe, Pamela
AU  - Saladino, Maria Laura
AU  - Sánchez Menoyo, José Luis
AU  - Shuey, Neil
AU  - Vucic, Steve
AU  - Shaw, Cameron
AU  - Deri, Norma
AU  - Arruda, Walter Oleschko
AU  - Butzkueven, Helmut
AU  - Spelman, Tim
AU  - Taylor, Bruce V
TI  - Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis
AID  - 10.1136/jnnp-2016-314013
DP  - 2016 Dec 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 1343--1349
VI  - 87
IP  - 12
4099  - http://jnnp.bmj.com/content/87/12/1343.short
4100  - http://jnnp.bmj.com/content/87/12/1343.full
SO  - J Neurol Neurosurg Psychiatry2016 Dec 01; 87
AB  - 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.