title: Identification of risk factors associated with onset and progression of amyotrophic lateral sclerosis using systematic review and meta-analysis.
abstract: Although amyotrophic lateral sclerosis (ALS) was identified as a neurological condition 150 years ago, risk factors related to the onset and progression of ALS remain largely unknown. Monogenic mutations in over 30 genes are associated with about 10% of ALS cases. The age at onset of ALS and disease types has been found to influence ALS progression. The present study was designed to identify additional putative risk factors associated with the onset and progression of ALS using systematic review and meta-analysis of observational studies. Risk factors that may be associated with ALS include: 1) genetic mutations, including the intermediate CAG repeat expansion in ATXN2; 2) previous exposure to heavy metals such as lead and mercury; 3) previous exposure to organic chemicals, such as pesticides and solvents; 4) history of electric shock; 5) history of physical trauma/injury (including head trauma/injury); 6) smoking (a weak risk factor for ALS in women); and 6) other risk factors, such as participating in professional sports, lower body mass index, lower educational attainment, or occupations requiring repetitive/strenuous work, military service, exposure to Beta-N-methylamino-l-alanin and viral infections. Risk factors that may be associated with ALS progression rate include: 1) nutritional status, including vitamin D deficiency; 2) comorbidities; 3) ethnicity and genetic factors; 4) lack of supportive care; and 4) smoking. The extent to which these associations may be causal is discussed, with further research recommended to strengthen the evidence on which determinations of causality may be based.
authors.affiliation: School of Epidemiology, Public Health and Preventive Medicine, Faculty of Medicine, University of Ottawa, ON K1H 8M5, Canada; School of Life Science, Changchun Normal University, Changchun, Jilin 130032, China. Electronic address: myang015@uottawa.ca.
authors.forename: Ming-Dong
authors.initials: MD
authors.lastname: Wang
authors.affiliation: School of Epidemiology, Public Health and Preventive Medicine, Faculty of Medicine, University of Ottawa, ON K1H 8M5, Canada.
authors.forename: Julian
authors.initials: J
authors.lastname: Little
authors.affiliation: McLaughlin Center for Population Risk Assessment, University of Ottawa, Ottawa, ON, Canada; Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, ON, Canada; Environmental Health Research Unit, Interdisciplinary School of Health Sciences University of Ottawa, 25 University Pvt., Ottawa, ON K1N 6N5, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Gomes
authors.affiliation: Brain Research Centre, Department of Medicine (Neurology), University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Cashman
authors.affiliation: School of Epidemiology, Public Health and Preventive Medicine, Faculty of Medicine, University of Ottawa, ON K1H 8M5, Canada; McLaughlin Center for Population Risk Assessment, University of Ottawa, Ottawa, ON, Canada; Risk Sciences International, Ottawa, ON, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Krewski
mesh_terms: D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D018450:Disease Progression; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009752:Nutritional Status; D010575:Pesticides / Q000633:toxicity; D012307:Risk Factors; D014808:Vitamin D Deficiency / Q000453:epidemiology
chemical_list: C000600133:ATXN2L protein, human; D009419:Nerve Tissue Proteins; D010575:Pesticides
keywords: Amyotrophic lateral sclerosis; Etiology; Meta-analysis; Onset; Progression; Risk factor; Systematic review