Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis
Chunrong Tao 1, Steve Simpson Jr 1, Ingrid van der Mei 1, Leigh Blizzard 1, Eva Havrdova 2, Dana Horakova 3, Vahid Shaygannejad 4, Alessandra Lugaresi 5 6, Guillermo Izquierdo 7, Maria Trojano 8, Pierre Duquette 9, Marc Girard 9, Franois Grand'Maison 10, Pierre Grammond 11, Raed Alroughani 12, Murat Terzi 13, Celia Oreja-Guevara 14, Seyed Aidin Sajedi 15, Gerardo Iuliano 16, Patrizia Sola 17, Jeannette Lechner-Scott 18, Vincent Van Pesch 19, Eugenio Pucci 20, Roberto Bergamaschi 21, Michael Barnett 22, Cristina Ramo 23, Bhim Singhal 24, Daniele LA Spitaleri 25, Mark Slee 26, Freek Verheul 27, Ricardo Fernández Bolaños 28, Maria Pia Amato 29, Edgardo Cristiano 30, Franco Granella 31, Suzanne Hodgkinson 32, Marcela Fiol 33, Orla Gray 34, Pamela McCombe 35, Maria Laura Saladino 36, José Luis Sánchez Menoyo 37, Neil Shuey 38, Steve Vucic 39, Cameron Shaw 40, Norma Deri 41, Walter Oleschko Arruda 42, Helmut Butzkueven 43 44, Tim Spelman 43, Bruce V Taylor 1; MSBase Study Group
Affiliations
Affiliations
- 1Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
- 2Department of Neurology, Faculty of Medicine, Center of Clinical Neuroscience, 1st General University Hospital and Charles University in Prague, Prague, Czech Republic.
- 3Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, General University Hospital, Prague, Czech Republic.
- 4Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
- 5Department of Biomedical and NeuroMotor Sciences (DIBINEM), Alma Mater Studiorum-Università di Bologna, Bologna, Italy.
- 6IRCCS Istituto delle Scienze Neurologiche-"UOSI Riabilitazione Sclerosi Multipla", Bologna, Italy.
- 7Hospital Universitario Virgen Macarena, Sevilla, Spain.
- 8Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
- 9CHUM-Hôpital Notre Dame, Montreal, Canada.
- 10Neuro Rive-Sud, Hôpital Charles LeMoyne, Quebec, Quebec, Canada.
- 11CISSS Chaudiere-Appalaches, Levis, Quebec, Canada.
- 12Amiri Hospital, Kuwait City, Kuwait.
- 13Department of Neurology, Mayis University, Samsun, Turkey.
- 14University Hospital San Carlos, IdISSC, Madrid, Spain.
- 15Department of Neurology, Golestan University of Medical Sciences, Gorgan, Iran.
- 16Ospedali Riuniti di Salerno, Salerno, Italy.
- 17Department of Neuroscience, Universitu of Modena e Reggio Emilia, Nuovo Ospedale Civile S. Agostino/Estense, Modena, Italy.
- 18John Hunter Hospital, University of Newcastle, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
- 19Cliniques Universitaires Saint-Luc, Brussels, Belgium.
- 20Neurology Unit, ASUR Marche-AV 3, Macerata, Italy.
- 21C. Mondino National Neurological Institute, Pavia, Italy.
- 22Brain and Mind Research Institute, Sydney, New South Wales, Australia.
- 23Hospital Germans Trias I Pujol, Badalona, Spain.
- 24Bombay Hospital Institute of Medical Sciences, Mumbai, India.
- 25AORN San Giuseppe Moscati Avellino, Avellino, Italy.
- 26Flinders University and Medical Centre, Adelaide, South Australia, Australia.
- 27Groene Hart Ziekenhuis, Gouda, The Netherlands.
- 28Hospital Universitario Virgen de Valme, Sevilla, Spain.
- 29Department of Neurofarba, Section of Neurosciences, University of Florence, Florence, Italy.
- 30Hospital Italiano, Buenos Aries, Argentina.
- 31Department of Neuroscience, University of Parma, Parma, Italy.
- 32Liverpool Hospital, Liverpool, New South Wales, Australia.
- 33FLENI, Buenos Aries, Argentina.
- 34Ulster Hospital, Dundonald, UK.
- 35St Andrew's Place, Brisbane, Australia.
- 36INEBA, Buenos Aries, Argentina.
- 37Hospital de Galdakao-Usansolo, Galdakao, Spain.
- 38St Vincent's Hospital, Melbourne, Victoria, Australia.
- 39Westmead Hospital, Sydney, New South Wales, Australia.
- 40Geelong Hospital, Geelong, Victoria, Australia.
- 41Hospital Fernandez, Capital Federal, Argentina.
- 42Hospital Ecoville, Curitiba, Brazil.
- 43Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
- 44Department of Neurology, Eastern Health, Monash University, Box Hill, Victoria, Australia.
Abstract
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.
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