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

I. A.F. Van Der Mei, Robyn M. Lucas, B. V. Taylor, P. C. Valery, T Dwyer, Trevor J. Kilpatrick, Michael P. Pender, D. Williams, C CHAPMAN, P. Otahal, Anne-Louise Ponsonby

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)461-469
Number of pages9
JournalMultiple Sclerosis
Issue number4
Publication statusPublished - 1 Apr 2016
Externally publishedYes


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