van der Mei, IAF and Lucas, RM and Taylor, BV and Valery, PC and Dwyer, T and Kilpatrick, TJ and Pender, MP and Williams, D and Chapman, C and Otahal, P and Ponsonby, AL, Population attributable fractions and joint effects of key risk factors for multiple sclerosis, Multiple Sclerosis Journal, 22, (4) pp. 461-469. ISSN 1352-4585 (2016) [Refereed Article]
© The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
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 Field:||Epidemiology not elsewhere classified|
|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)|
|Year Published:||2016 (online first 2015)|
|Web of Science® Times Cited:||37|
|Deposited By:||Menzies Institute for Medical Research|
Repository Staff Only: item control page