title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, United States.
authors.forename: Milena A
authors.initials: MA
authors.lastname: Gianfrancesco
authors.affiliation: Kaiser Permanente Division of Research, Oakland, CA, United States.
authors.forename: Brigid
authors.initials: B
authors.lastname: Acuna
authors.affiliation: Kaiser Permanente Division of Research, Oakland, CA, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Division of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, United States.
authors.forename: Farren B S
authors.initials: FB
authors.lastname: Briggs
authors.affiliation: Division of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Quach
authors.affiliation: Kaiser Permanente Division of Research, Oakland, CA, United States.
authors.forename: Kalliope H
authors.initials: KH
authors.lastname: Bellesis
authors.affiliation: Palm Drive Hospital, Sebastopol, CA, United States.
authors.forename: Allan
authors.initials: A
authors.lastname: Bernstein
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Hedstrom
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: Kaiser Permanente Division of Research, Oakland, CA, United States.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Division of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, United States; Kaiser Permanente Division of Research, Oakland, CA, United States. Electronic address: lbarcellos@genepi.berkeley.edu.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
mesh_terms: D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D049628:Body Size; D002140:California; D002648:Child; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000209:etiology*; D009765:Obesity / Q000209:etiology*; D016017:Odds Ratio; D063766:Pediatric Obesity / Q000150:complications; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
keywords: Adolescence; Childhood; Genetics; Multiple sclerosis; Risk factors in epidemiology