title: Genetic background of multiple sclerosis.
abstract: Multiple sclerosis (MS) is a one of the group of diseases labeled as "common complex". Virtually all common complex traits, genetic and environmental components have important roles, both independently and interactively, in disease susceptibility and stochastic and epigenetic effects cannot be overlooked. Data presented are largely part of the Canada-wide prospective, population-based longitudinal Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS) which includes over 30,000 unique families having at least 1 member with MS. Findings do not support a general propensity to autoimmune disease in MS families, but clearly highlight the importance of controlling for gender (patient, informant) when conducting such studies. The MHC class II association has been fine-mapped to the HLA-DRB5*0101-HLA-DRB1*1501-HLA-DQA1*0102-HLA-DQB1*0602 extended haplotype. This HLA haplotype confers a relative risk of approximately 3 and homozygosity for this haplotype increases the risk by over 6 fold. However, the HLA haplotype loci interactions are complex and include, epistasis, trans and cis effects, and parent-of-origin effects. As well, there may be interactions of EBV and vitamin D with the HLA, In conclusion, using MS as an example, susceptibility for common complex disease most likely results from interactions of genes, environmental interactions and gene/environment interactions.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada. sadovnik@infinet.net
authors.forename: A Dessa
authors.initials: AD
authors.lastname: Sadovnick
mesh_terms: D002170:Canada; D004843:Epistasis, Genetic; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D059811:HLA-DRB1 Chains / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D020412:Multifactorial Inheritance; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D012306:Risk; D012737:Sex Factors; D014807:Vitamin D / Q000276:immunology
chemical_list: D059811:HLA-DRB1 Chains; D014807:Vitamin D