BBB Seminar: Georg Ebers
The cause of multiple sclerosis
Wellcome Trust Centre for Human Genetics and Department of Clinical Neurology, John Radcliffe Hospital, University of Oxford, UK
The genetic epidemiology of multiple sclerosis (MS) has been painstakingly worked out over the last 25 years. The evidence is overwhelming for several firm conclusions to be made. MS is determined by gene-environment interaction, and the genetic portion is very largely determined by what happens at the major histocompatibility complex. This has been somewhat occult but once epistasis and epigenetics are taken into account, this constitutes the majority of the genetic risks. The environmental portion of the disease, which surely accounts for most of the disease geography, appears to represent and be characterised by gene-environment interaction, mediated by epigenetic change. There are four specific environmental factors for which the evidence is quite strong, but the most influential of these in northern Europe appears more and more to be the consequences of vitamin D insufficiency/sufficiency. Timing of the environment appears to have at least three epochs. Month-of-birth studies have been largely neglected in disease but of course they have been extremely important in giving broad hints as to the nature of environmental factors. We review the genetics including specific genes and their interactions, the environment and specific interactions, and propose a new disease paradigm supported by evidence, for the pathogenesis of the disease which can explain the observed facts.
Host: Karen Blaauw Helle, Department of Biomedicine