title: Identifying disease modifying genes in multiple sclerosis.
abstract: Evidence is mounting that genetic variation influences not only susceptibility to multiple sclerosis (MS), but also its course and severity. Identification of disease modifying genes, however, poses unique challenges, especially on how to classify the course and outcome of the disease in ways that may be relevant to analysis of biological factors that might be influenced by genes. The power of the statistical approaches to detect small effects of individual genes in complex disorders such as MS is problematic, and approaches to estimate power must be appropriate for the data. Nonetheless, using contemporary schemes of classification, genetic variants that influence disease course have been found; in fact, a small number have been confirmed to influence disease course in two or more independent studies. This review addresses strategies relevant to identification of disease modifying genes in MS, and summarizes and critically evaluates the current state of knowledge in this area.
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, 200 First Street, SW, Rochester, MN 55905, USA.
authors.forename: Orhun H
authors.initials: OH
authors.lastname: Kantarci
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics; D008040:Genetic Linkage; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D012795:Sialoglycoproteins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D006684:HLA-DR Antigens; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha