title: Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis.
abstract: Genetic predisposition to multiple sclerosis (MS) only explains a fraction of the disease risk; lifestyle and environmental factors are key contributors to the risk of MS. Importantly, these nongenetic factors can influence pathogenetic pathways, and some of them can be modified. Besides established MS-associated risk factors - high latitude, female sex, smoking, low vitamin D levels caused by insufficient sun exposure and/or dietary intake, and Epstein-Barr virus (EBV) infection - strong evidence now supports obesity during adolescence as a factor increasing MS risk. Organic solvents and shift work have also been reported to confer increased risk of the disease, whereas factors such as use of nicotine or alcohol, cytomegalovirus infection and a high coffee consumption are associated with a reduced risk. Certain factors - smoking, EBV infection and obesity - interact with HLA risk genes, pointing at a pathogenetic pathway involving adaptive immunity. All of the described risk factors for MS can influence adaptive and/or innate immunity, which is thought to be the main pathway modulated by MS risk alleles. Unlike genetic risk factors, many environmental and lifestyle factors can be modified, with potential for prevention, particularly for people at the greatest risk, such as relatives of individuals with MS. Here, we review recent data on environmental and lifestyle factors, with a focus on gene-environment interactions.
authors.affiliation: Neuroimmunology Unit, Center for Molecular Medicine, L8:04, Karolinska University Hospital (Solna), 17176 Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: Genetic Epidemiology and Genomics Laboratory, California Institute for Quantitative Biosciences (QB3), Office: 308D Stanley Hall, University of California, Berkeley, CA 94720-3220.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
mesh_terms: D004781:Environmental Exposure / Q000009:adverse effects*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D009103:Multiple Sclerosis / Q000209:etiology*; D012307:Risk Factors