Gavin Giovannoni1, George Ebers. 1. Institute of Cell and Molecular Science, Queen Mary University London, London, UK. g.giovannoni@qmul.ac.uk
Abstract
PURPOSE OF REVIEW: We review current thinking on the aetiology of multiple sclerosis, how genetic susceptibility interacts with environmental risk factors at the population level, multiple sclerosis-associated risk factors and contemporary causation theory. RECENT FINDINGS: Two large genomic studies have confirmed the unambiguous associations with the DRB1 and DQB alleles of the human leucocyte antigen class II region. No other region with genome-wide significance has been identified. Family-based genetic epidemiological approaches have found no evidence of nongenetic transmissibility. This indicates that the action of the environment in influencing multiple sclerosis risk is operative at a macroenvironmental or population level, and not within families or the microenvironment. Environmental factors receiving renewed attention include vitamin D status, Epstein-Barr virus infection and smoking. Bradford Hill's criteria for causation have been modified and should be adopted as a framework for demonstrating causation in relationship to multiple sclerosis. SUMMARY: Multiple sclerosis is a complex disease because of interaction between genes and the environment. Any theory of causation for a specific agent will have to be congruent with the biology of the disease.
PURPOSE OF REVIEW: We review current thinking on the aetiology of multiple sclerosis, how genetic susceptibility interacts with environmental risk factors at the population level, multiple sclerosis-associated risk factors and contemporary causation theory. RECENT FINDINGS: Two large genomic studies have confirmed the unambiguous associations with the DRB1 and DQB alleles of the human leucocyte antigen class II region. No other region with genome-wide significance has been identified. Family-based genetic epidemiological approaches have found no evidence of nongenetic transmissibility. This indicates that the action of the environment in influencing multiple sclerosis risk is operative at a macroenvironmental or population level, and not within families or the microenvironment. Environmental factors receiving renewed attention include vitamin D status, Epstein-Barr virus infection and smoking. Bradford Hill's criteria for causation have been modified and should be adopted as a framework for demonstrating causation in relationship to multiple sclerosis. SUMMARY:Multiple sclerosis is a complex disease because of interaction between genes and the environment. Any theory of causation for a specific agent will have to be congruent with the biology of the disease.
Authors: Michele Mishto; Elena Bellavista; Claudia Ligorio; Kathrin Textoris-Taube; Aurelia Santoro; Mara Giordano; Sandra D'Alfonso; Florinda Listì; Benedetta Nacmias; Elena Cellini; Maurizio Leone; Luigi M E Grimaldi; Chiara Fenoglio; Federica Esposito; Filippo Martinelli-Boneschi; Daniela Galimberti; Elio Scarpini; Ulrike Seifert; Maria Pia Amato; Calogero Caruso; Maria P Foschini; Peter M Kloetzel; Claudio Franceschi Journal: PLoS One Date: 2010-02-18 Impact factor: 3.240