Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis.


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.

DOI: 10.1136/jnnp-2016-314013

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@article{Tao2016HigherLI, title={Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis.}, author={Chunrong Tao and Steve Simpson and Ingrid A F van der Mei and Leigh C Blizzard and Eva Kubala Havrdov{\'a} and D Horakova and Vahid Shaygannejad and Alessandra Lugaresi and Guillermo Izquierdo and Mar{\'i}a Trojano and Pierre Duquette and Marc Girard and Franois Grand'Maison and Pierre Grammond and Raed Alroughani and Murat Terzi and Celia Oreja-Guevara and Seyed Aidin Sajedi and Gerardo Iuliano and Patrizia Sola and Jeannette S. Lechner-Scott and Vincent van Pesch and Eugenio Pucci and Roberto Bergamaschi and Michael Harry Barnett and Cristina Ramo and Bhim Sen Singhal and Daniele La Spitaleri and Mark Slee and Freek Verheul and Ricardo Fern{\'a}ndez Bola{\~n}os and Maria Pia Amato and Edgardo Cristiano and Franco Granella and Suzanne J. Hodgkinson and Marcela P Fiol and Orla M Gray and Pamela A. McCombe and Maria Laura Saladino and Jos{\'e} Luis S{\'a}nchez Menoyo and Neil H Shuey and S Vucic and Cameron P Shaw and Norma Deri and Walter Oleschko Arruda and Helmut Butzkueven and Tim D Spelman and Bruce V Taylor}, journal={Journal of neurology, neurosurgery, and psychiatry}, year={2016}, volume={87 12}, pages={1343-1349} }