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.

Item Type:	Refereed Article
Keywords:	first demyelinating event, gene-environment interaction, multiple sclerosis, population attributable fraction, risk factors
Research Division:	Health Sciences
Research Group:	Epidemiology
Research Field:	Epidemiology not elsewhere classified
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	van der Mei, IAF (Professor Ingrid van der Mei)
UTAS Author:	Taylor, BV (Professor Bruce Taylor)
UTAS Author:	Otahal, P (Mr Petr Otahal)
ID Code:	102091
Year Published:	2016 (online first 2015)
Web of Science® Times Cited:	37
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2015-07-28
Last Modified:	2017-11-03
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