Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors

Abstract

Objective: To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors.

Methods: Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied.

Results: In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.60×10(-4)), and a twofold risk of MS for females with a BMI≥30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles.

Interpretation: Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors.

Keywords: Adolescence; Childhood; Genetics; Multiple sclerosis; Risk factors in epidemiology.

Figure 1

Multivariate adjusted odds ratios and 95% CIs for body size/mass and MS susceptibility in females at different time periods. Stratified odds ratios are presented for MS cases with age of onset between 20–29 years of age, and those with age at onset at 30 years old or later. Black circles reflect odds of MS amongst females reporting being a little/very overweight at age 10. White squares demonstrate odds of MS amongst females reporting being a little/very overweight at age 20. Asterisk indicates p-value <0.05.