Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis

• Published in: Nature reviews. Neurology Vol. 13; no. 1; pp. 25 - 36
• Main Authors: Olsson, Tomas, Barcellos, Lisa F., Alfredsson, Lars
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2017; Nature Publishing Group
• Subjects: 631/208/727/2000; 692/499; 692/699/375/1411/1666; 692/700/459; Cytomegalovirus; Disease; Environmental aspects; Epidemiology; Genes; Genetic aspects; Genomics; Health risk assessment; Infections; Lifestyles; Medicin och hälsovetenskap; Medicine & Public Health; Multiple sclerosis; Neurology; review-article; Risk factors; United States > US; Sweden; California
• ISSN: 1759-4758; 1759-4766; 1759-4766
• DOI: 10.1038/nrneurol.2016.187

Key Points Epstein–Barr virus (EBV) infection, smoking, low vitamin D and lack of sun exposure are well established factors associated with risk of multiple sclerosis (MS); recently, adolescent obesity has been added to this list Less established factors include exposure to organic solvents and night shift work, which associate with increased risk, whereas oral tobacco use, cytomegalovirus infection, alcohol use and coffee consumption associate with decreased risk Some of these factors should be considered in primary prevention Most lifestyle and environmental factors seem to have the greatest effect during a particular time window — adolescence Certain factors, such as EBV infection, smoking and adolescent obesity interact with human leukocyte antigen MS risk genes, with substantial risk increases in individuals who carry genes that predispose them to MS The interaction with these immune response genes provides strong evidence that these lifestyle and environmental factors act on adaptive immunity, leading to autoimmune attack on the nervous system Lifestyle and environmental factors, some which are potentially modifiable, have important roles in the risk of multiple sclerosis (MS), and some of these risk factors, such as Epstein–Barr virus infection, smoking and obesity in adolescence, interact with genetic risk factors. Here, Olsson and colleagues summarize recent data on modifiable environmental and lifestyle factors in MS, with a focus on gene–environment interactions. 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.