In a Swedish population-based case-control study (1571 cases, 3371 controls), subjects with different body mass indices (BMIs) were compared regarding multiple sclerosis (MS) risk, by calculating odds ratios (OR) with 95% confidence intervals (95% CI). Subjects whose BMI exceeded 27 kg/m² at age 20 had a two-fold increased risk of developing MS compared with normal weight subjects. Speculatively, the obesity epidemic may explain part of the increasing MS incidence as recorded in some countries. Measures taken against adolescent obesity may thus be a preventive strategy against MS.

Objective: The aim of this study was to estimate the influence of tobacco smoking and Swedish snuff use on the risk of developing multiple sclerosis (MS). Methods: A population-based case-control study was performed in Sweden, using incident cases of MS (902 cases and 1,855 controls). A case was defined as a subject from the study base who had received a diagnosis of MS, and controls were randomly selected from the study base. The incidence of MS among smokers was compared with that of never-smokers. We also investigated whether the use of Swedish snuff had an impact on the risk of developing MS. Results: Smokers of both sexes had an increased risk of developing MS (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.2–1.7 for women, and OR 1.8, 95% CI 1.3–2.5 for men). The increased risk was apparent even among subjects who had previously smoked moderately (≤5 pack-years) prior to index, and the risk increased with increasing cumulative dose (p < 0.0001). The increased risk for MS associated with smoking remained up to 5 years after stopping smoking. In contrast, taking Swedish snuff for more than 15 years decreased the risk of developing MS (OR 0.3, 95% CI 0.1–0.8). Conclusions: Smokers of both sexes run an increased risk of developing multiple sclerosis (MS), and the risk increases with cumulative dose of smoking. However, the use of Swedish snuff is not associated with elevated risk for MS, which may indicate that nicotine is not the substance responsible for the increased risk of developing MS among smokers.

Both genetic and environmental factors display low or modest associations with multiple sclerosis. Hypothetically, gene–environment interactions may exert much stronger effects. In this study, we investigated potential interactions between genetic risk factors and smoking in relation to risk of developing multiple sclerosis. A population-based case–control study involving incident cases of multiple sclerosis (843 cases, 1209 controls) was performed in Sweden. Cases and controls were classified according to their smoking status and human leukocyte antigen DRB1 as well as human leukocyte antigen A genotypes. Subjects with different genotypes and smoking habits were compared with regard to incidence of multiple sclerosis, by calculating odds ratios with 95% confidence intervals employing logistic regression. The potential interaction between different genotypes, as well as between genotype and smoking, was evaluated by calculating attributable proportion due to interaction. A significant interaction between two genetic risk factors, carriage of human leukocyte antigen DRB1*15 and absence of human leukocyte antigen A*02, was observed among smokers whereas such an interaction was absent among non-smokers. There were considerable differences in odds ratios between the various groups. Compared with non-smokers with neither of the genetic risk factors, the odds ratio was 13.5 (8.1–22.6) for smokers with both genetic risk factors. The odds ratio for smokers without genetic risk was 1.4 (0.9–2.1) and the odds ratio for non-smokers with both genetic risk factors was 4.9 (3.6–6.6). Among those with both genetic risk factors, smoking increased the risk by a factor of 2.8 in comparison with a factor of 1.4 among those without the genetic risk factors. The risk of developing multiple sclerosis associated with human leukocyte antigen genotypes may be strongly influenced by smoking status. The findings are consistent with our hypothesis that priming of the immune response in the lungs may subsequently lead to multiple sclerosis in genetically susceptible people.

Objective: We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS). Methods: We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with prevalent cases (937 cases, 609 controls). Subjects with different genotypes and BMI were compared with regard to incidence of MS by calculating odds ratios (ORs) with 95% confidence intervals (CIs) employing logistic regression. Potential interactions between genotypes and BMI were evaluated by calculating the attributable proportion due to interaction. Results: In both cohorts, a significant interaction was observed between HLA-DRB1*15 and obesity, regardless of HLA-A*02 status. Similarly, there was a significant interaction between absence of A*02 and obesity, regardless of DRB1*15 status. In the incident cohort, obese subjects with the most susceptible genotype (carriage of DRB1*15 and absence of A*02) had an OR of 16.2 (95% CI 7.5–35.2) compared to nonobese subjects without the genetic risk factors. The corresponding OR in the prevalent study was 13.8 (95% CI 4.1–46.8). Conclusions: We observed striking interactions between BMI status and HLA genotype with regard to MS risk. Hypothetically, a low-grade inflammatory response inherent to obesity synergizes with the adaptive, HLA molecule–restricted arm of the immune system, causing MS. Prevention of adolescent obesity may thus lower the risk of developing MS, predominantly among people with a genetic susceptibility to the disease.

Smoking is one of the most established risk factors for multiple sclerosis (MS). The aim of this study was to investigate how age at smoking debut, duration, intensity and cumulative dose of smoking, and smoking cessation influence the association between smoking and MS risk. In two Swedish population-based case–control studies (7,883 cases, 9,264 controls), subjects with different smoking habits were compared regarding MS risk, by calculating odds ratios with 95 % confidence intervals. We observed a clear dose response association between cumulative dose of smoking and MS risk (p value for trend <10⁻³⁵). Both duration and intensity of smoking contributed independently to the increased risk of MS. However, the detrimental effect of smoking abates a decade after smoking cessation regardless of the cumulative dose of smoking. Age at smoking debut did not affect the association between smoking and MS. Smoking increases the risk of MS in a dose response manner. However, in contrary to several other risk factors for MS that seem to affect the risk only if the exposure takes place during a specific period in life, smoking affects MS risk regardless of age at exposure, and the detrimental effect slowly abates after smoking cessation.