TY - JOUR T1 - Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 1343 LP - 1349 DO - 10.1136/jnnp-2016-314013 VL - 87 IS - 12 AU - Chunrong Tao AU - Steve Simpson, Jr AU - Ingrid van der Mei AU - Leigh Blizzard AU - Eva Havrdova AU - Dana Horakova AU - Vahid Shaygannejad AU - Alessandra Lugaresi AU - Guillermo Izquierdo AU - Maria Trojano AU - Pierre Duquette AU - Marc Girard AU - Franois Grand'Maison AU - Pierre Grammond AU - Raed Alroughani AU - Murat Terzi AU - Celia Oreja-Guevara AU - Seyed Aidin Sajedi AU - Gerardo Iuliano AU - Patrizia Sola AU - Jeannette Lechner-Scott AU - Vincent Van Pesch AU - Eugenio Pucci AU - Roberto Bergamaschi AU - Michael Barnett AU - Cristina Ramo AU - Bhim Singhal AU - Daniele LA Spitaleri AU - Mark Slee AU - Freek Verheul AU - Ricardo Fernández Bolaños AU - Maria Pia Amato AU - Edgardo Cristiano AU - Franco Granella AU - Suzanne Hodgkinson AU - Marcela Fiol AU - Orla Gray AU - Pamela McCombe AU - Maria Laura Saladino AU - José Luis Sánchez Menoyo AU - Neil Shuey AU - Steve Vucic AU - Cameron Shaw AU - Norma Deri AU - Walter Oleschko Arruda AU - Helmut Butzkueven AU - Tim Spelman AU - Bruce V Taylor Y1 - 2016/12/01 UR - http://jnnp.bmj.com/content/87/12/1343.abstract N2 - 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. ER -