University Of Tasmania

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

journal contribution
posted on 2023-05-18, 12:00 authored by Ingrid van der MeiIngrid van der Mei, Lucas, RM, Bruce TaylorBruce Taylor, Valery, PC, Dwyer, T, Kilpatrick, TJ, Pender, MP, Williams, D, Chapman, C, Petr OtahalPetr Otahal, Ponsonby, AL
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.


Publication title

Multiple Sclerosis Journal










Menzies Institute for Medical Research


Sage Publications Ltd.

Place of publication

United Kingdom

Rights statement

© The Author(s), 2015. Reprints and permissions: journalsPermissions.nav

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified