Contributions
Abstract: 207
Type: Oral
Genetic predisposition for Multiple Sclerosis (MS) only explains a fraction of the heritability of disease risk. Plausible explanations include numerous risk genes with very small effects, epigenetic regulation, gene-gene interactions, and gene-environment interactions. Environmental factors such as high latitude, smoking, low vitamin D levels caused by insufficient sun exposure and/or dietary intake, and viral infections are known to affect the risk of MS. Additional lifestyle exposures have been implicated in MS, with organic solvents, night shift work, and obesity during adolescence associating with increased risk and use of nicotine or alcohol, a high coffee consumption, and cytomegalovirus infection associating with reduced risk.
We have detailed genetic and lifestyle and environmental data in an extensive population-based MS case-control material (~12 000 cases and ~8000 controls) that enable us to study interactions between genetic and environmental factors. By selecting the major genetic MS risk alleles (HLA-A*02 and DRB1*15:01) and evaluating their relationship with strong environmental risk factors for MS such as Epstein-Barr virus infection, smoking, and obesity, striking gene-environment interactions become apparent. For example, HLA-A*02 negative and DRB1*15:01 positive Scandinavians that smoke have a 20-fold increase in MS risk, while their non-smoking counterpart have a 5-fold risk increase. These interactions between environment and HLA risk genes supports a pathogenetic role for adaptive immunity, which together with innate immunity is thought to be a key pathway modulated by MS risk alleles.
Genetic association studies in MS should be integrated with lifestyle and environmental data to completely understand the effects of interacting mechanisms. These non-genetic factors are key since, unlike genetic risk factors, many environmental and lifestyle factors can be modified and thereby influence pathogenetic pathways. Altering exposures that interact with the genetic predisposition to develop MS have the potential to help prevent disease, particularly for people at the greatest risk, such as relatives of individuals with MS.
Disclosure: The author has no conflict of interest and is funded by MS-forskningsfonden (MS research fund), Neuroförbundet (Neuro Sweden), and The Lars Hierta Memorial Foundation.
Abstract: 207
Type: Oral
Genetic predisposition for Multiple Sclerosis (MS) only explains a fraction of the heritability of disease risk. Plausible explanations include numerous risk genes with very small effects, epigenetic regulation, gene-gene interactions, and gene-environment interactions. Environmental factors such as high latitude, smoking, low vitamin D levels caused by insufficient sun exposure and/or dietary intake, and viral infections are known to affect the risk of MS. Additional lifestyle exposures have been implicated in MS, with organic solvents, night shift work, and obesity during adolescence associating with increased risk and use of nicotine or alcohol, a high coffee consumption, and cytomegalovirus infection associating with reduced risk.
We have detailed genetic and lifestyle and environmental data in an extensive population-based MS case-control material (~12 000 cases and ~8000 controls) that enable us to study interactions between genetic and environmental factors. By selecting the major genetic MS risk alleles (HLA-A*02 and DRB1*15:01) and evaluating their relationship with strong environmental risk factors for MS such as Epstein-Barr virus infection, smoking, and obesity, striking gene-environment interactions become apparent. For example, HLA-A*02 negative and DRB1*15:01 positive Scandinavians that smoke have a 20-fold increase in MS risk, while their non-smoking counterpart have a 5-fold risk increase. These interactions between environment and HLA risk genes supports a pathogenetic role for adaptive immunity, which together with innate immunity is thought to be a key pathway modulated by MS risk alleles.
Genetic association studies in MS should be integrated with lifestyle and environmental data to completely understand the effects of interacting mechanisms. These non-genetic factors are key since, unlike genetic risk factors, many environmental and lifestyle factors can be modified and thereby influence pathogenetic pathways. Altering exposures that interact with the genetic predisposition to develop MS have the potential to help prevent disease, particularly for people at the greatest risk, such as relatives of individuals with MS.
Disclosure: The author has no conflict of interest and is funded by MS-forskningsfonden (MS research fund), Neuroförbundet (Neuro Sweden), and The Lars Hierta Memorial Foundation.