title: Population attributable fractions and joint effects of key risk factors for multiple sclerosis.
abstract: OBJECTIVE
  We examined the combined effect of having multiple key risk factors and the interactions between the key risk factors of multiple sclerosis (MS).
  
  
  METHODS
  We performed an incident case-control study including cases with a first clinical diagnosis of central nervous system demyelination (FCD) and population-based controls.
  
  
  RESULTS
  Compared to those without any risk factors, those with one, two, three, and four or five risk factors had increased odds of being an FCD case of 2.12 (95% confidence interval (CI), 1.11-4.03), 4.31 (95% CI, 2.24-8.31), 7.96 (95% CI, 3.84-16.49), and 21.24 (95% CI, 5.48-82.40), respectively. Only HLA-DR15 and history of infectious mononucleosis interacted significantly on the additive scale (Synergy index, 3.78; p = 0.03). The five key risk factors jointly accounted for 63.8% (95% CI, 43.9-91.4) of FCD onset. High anti-EBNA IgG was another important contributor.
  
  
  CONCLUSIONS
  A high proportion of FCD onset can be explained by the currently known risk factors, with HLA-DR15, ever smoking and low cumulative sun exposure explaining most. We identified a significant interaction between HLA-DR15 and history of IM in predicting an FCD of CNS demyelination, which together with previous observations suggests that this is a true interaction.
authors.affiliation: Menzies Research Institute, Australia Ingrid.vanderMei@utas.edu.au.
authors.forename: Iaf
authors.initials: I
authors.lastname: van der Mei
authors.affiliation: National Centre for Epidemiology and Population Health, The Australian National University, Australia.
authors.forename: R M
authors.initials: RM
authors.lastname: Lucas
authors.affiliation: Menzies Research Institute, Australia.
authors.forename: B V
authors.initials: BV
authors.lastname: Taylor
authors.affiliation: Queensland Institute of Medical Research, Australia.
authors.forename: P C
authors.initials: PC
authors.lastname: Valery
authors.affiliation: International Agency for Research on Cancer, France.
authors.forename: T
authors.initials: T
authors.lastname: Dwyer
authors.affiliation: Centre for Neuroscience, The University of Melbourne, Australia.
authors.forename: T J
authors.initials: TJ
authors.lastname: Kilpatrick
authors.affiliation: Department of Neurophysiology, John Hunter Hospital, Australia.
authors.forename: M P
authors.initials: MP
authors.lastname: Pender
authors.affiliation: Department of Neurophysiology, John Hunter Hospital, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Williams
authors.affiliation: Department of Neurology, Barwon Health, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Chapman
authors.affiliation: Menzies Research Institute, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Otahal
authors.affiliation: Murdoch Childrens Research Institute, Australia.
authors.forename: A-L
authors.initials: AL
authors.lastname: Ponsonby
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001315:Australia / Q000453:epidemiology; D016022:Case-Control Studies; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D059647:Gene-Environment Interaction; D059810:HLA-DR Serological Subtypes / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D015994:Incidence; D007244:Infectious Mononucleosis / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D012621:Seasons; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D013472:Sunlight; D013997:Time Factors; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D007074:Immunoglobulin G
keywords: First demyelinating event; gene-environment interaction; multiple sclerosis; population attributable fraction; risk factors