Population attributable fractions and joint effects of key risk factors for multiple sclerosis

• Published in: Multiple sclerosis 2016-04, Vol.22 (4), p.461-469
• Main Authors: van der Mei, IAF, Lucas, RM, Taylor, BV, Valery, PC, Dwyer, T, Kilpatrick, TJ, Pender, MP, Williams, D, Chapman, C, Otahal, P, Ponsonby, A-L
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibodies, Viral - blood; Australia - epidemiology; Case-Control Studies; Central nervous system; Demyelination; Epstein-Barr Virus Nuclear Antigens - immunology; Female; Gene-Environment Interaction; Health risk assessment; HLA-DR Serological Subtypes - genetics; HLA-DR Serological Subtypes - immunology; Humans; Immunoglobulin G; Immunoglobulin G - blood; Incidence; Infectious mononucleosis; Infectious Mononucleosis - epidemiology; Logistic Models; Male; Middle Aged; Mononucleosis; Multiple sclerosis; Multiple Sclerosis - diagnosis; Multiple Sclerosis - epidemiology; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Multivariate Analysis; Odds Ratio; Polymorphism, Single Nucleotide; Prevalence; Risk Assessment; Risk Factors; Seasons; Smoking; Smoking - adverse effects; Smoking - epidemiology; Sun; Sunlight; Time Factors; Young Adult
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458515594040

Aim: 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.