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Review
. 2019 Sep;6(9):1905-1922.
doi: 10.1002/acn3.50862. Epub 2019 Aug 7.

Environmental and genetic risk factors for MS: an integrated review

Emmanuelle Waubant  1 , Robyn Lucas  2 , Ellen Mowry  3 , Jennifer Graves  4 , Tomas Olsson  5 , Lars Alfredsson  6 , Annette Langer-Gould  7
Affiliations
Review

Environmental and genetic risk factors for MS: an integrated review

Emmanuelle Waubant et al. Ann Clin Transl Neurol. 2019 Sep.

Abstract

Recent findings have provided a molecular basis for the combined contributions of multifaceted risk factors for the onset of multiple sclerosis (MS). MS appears to start as a chronic dysregulation of immune homeostasis resulting from complex interactions between genetic predispositions, infectious exposures, and factors that lead to pro-inflammatory states, including smoking, obesity, and low sun exposure. This is supported by the discovery of gene-environment (GxE) interactions and epigenetic alterations triggered by environmental exposures in individuals with particular genetic make-ups. It is notable that several of these pro-inflammatory factors have not emerged as strong prognostic indicators. Biological processes at play during the relapsing phase of the disease may result from initial inflammatory-mediated injury, while risk factors for the later phase of MS, which is weighted toward neurodegeneration, are not yet well defined. This integrated review of current evidence guides recommendations for clinical practice and highlights research gaps.

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Conflict of interest statement

E. Waubant has not received any pharmaceutical company honorarium. She is site PI for a Novartis and Roche trial. She has volunteered on an advisory board for a Novartis trial. She is a non‐remunerated advisor for clinical trial design to Novartis, Biogen‐IDEC, Sanofi, Genentech, Serono and Celgene. She has funding from the NIH, NMSS, PCORI, and the Race to Erase MS. She is the section editor for Annals of Clinical and Translational Neurology, and co‐Chief editor for MSARD. R.M. Lucas has not received any pharmaceutical company honoraria. She was an invited speaker at CMSC 2018, with travel and accommodation paid. She received funding from MS Research Australia and the National Health and Medical Research Council of Australia. Her salary is part‐funded through a National Health and Medical Research Council of Australia Senior Research Fellowship. E. Mowry receives research support from Biogen and Genzyme. She was site PI for clinical studies sponsored by Biogen and Sun Pharma. Teva Neuroscience provides free medication for a clinical trial, of which she is PI. Dr. Mowry receives honoraria for editorial duties for UpToDate. J. Graves has received honoraria for non‐promotional, unbranded educational seminar speaking for Biogen and Genzyme. She has research support from Biogen and Genentech. T. Olsson has received unrestricted MS research grants, and/or compensation for lectures and advisory boards from Biogen, Novartis, Genzyme, Roche and Merck. L. Alfredsson receives research support from the Swedish Research Council and the Swedish Research Council for Health, Working life and Welfare. He has received speakers honoraria from Teva and Biogen. A. Langer‐Gould reports grants from National Institutes of Health, grants from Patient Centered Outcomes Research Institute, grants from National MS Society, non‐financial support from European Congress for Treatment and Research in MS (ECTRIMS), non‐financial support from Institute for Clinical and Economic Review, other from Biogen, from Roche, outside the submitted work.

Figures

Figure 1
Figure 1
Environmental contributions to multiple sclerosis (MS) risk
See this image and copyright information in PMC

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