Tomas Olsson1, Jan Hillert. 1. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. Tomas.Olsson@ki.se
Abstract
PURPOSE OF REVIEW: We review the current thinking on the genetic aetiology of multiple sclerosis, new aspects of the influence of genes within the human leucocyte antigen (HLA) complex, how discrete non-HLA genes regulating multiple sclerosis start to be unequivocally demonstrated, and how knowledge from the genetics of experimental models of multiple sclerosis can be used. RECENT FINDINGS: Different alleles of the class II molecules display a hierarchy of risks including protective effects in multiple sclerosis. In addition, HLA class I genes are associated with the disease. Experimental multiple sclerosis models are regulated by many genes with small effects, more than about 100. Studies in humans suggest a similar situation. Indeed, the two genes unequivocally established, IL2RA and IL7RA, display a low odds ratio in the order of 1.3. We envisage that many more genes of this kind may be unravelled in the years to come. SUMMARY: There are hierarchies of influences from class II genes. Class I genes regulate disease as well. The unambiguous demonstration of non-HLA genes also suggests that many other genes impacting multiple sclerosis can be deciphered in the years to come. A complete knowledge of the most important of these may pave the way for more selective therapy and gene-environment studies.
PURPOSE OF REVIEW: We review the current thinking on the genetic aetiology of multiple sclerosis, new aspects of the influence of genes within the human leucocyte antigen (HLA) complex, how discrete non-HLA genes regulating multiple sclerosis start to be unequivocally demonstrated, and how knowledge from the genetics of experimental models of multiple sclerosis can be used. RECENT FINDINGS: Different alleles of the class II molecules display a hierarchy of risks including protective effects in multiple sclerosis. In addition, HLA class I genes are associated with the disease. Experimental multiple sclerosis models are regulated by many genes with small effects, more than about 100. Studies in humans suggest a similar situation. Indeed, the two genes unequivocally established, IL2RA and IL7RA, display a low odds ratio in the order of 1.3. We envisage that many more genes of this kind may be unravelled in the years to come. SUMMARY: There are hierarchies of influences from class II genes. Class I genes regulate disease as well. The unambiguous demonstration of non-HLA genes also suggests that many other genes impacting multiple sclerosis can be deciphered in the years to come. A complete knowledge of the most important of these may pave the way for more selective therapy and gene-environment studies.
Authors: Anna Karin Hedström; Izaura Lima Bomfim; Lisa Barcellos; Milena Gianfrancesco; Catherine Schaefer; Ingrid Kockum; Tomas Olsson; Lars Alfredsson Journal: Neurology Date: 2014-02-05 Impact factor: 9.910
Authors: Anna Karin Hedström; Izaura Lima Bomfim; Lisa F Barcellos; Farren Briggs; Catherine Schaefer; Ingrid Kockum; Tomas Olsson; Lars Alfredsson Journal: Int J Epidemiol Date: 2014-10-15 Impact factor: 7.196
Authors: Anna Karin Hedström; Michail Katsoulis; Ola Hössjer; Izaura L Bomfim; Annette Oturai; Helle Bach Sondergaard; Finn Sellebjerg; Henrik Ullum; Lise Wegner Thørner; Marte Wendel Gustavsen; Hanne F Harbo; Dragana Obradovic; Milena A Gianfrancesco; Lisa F Barcellos; Catherine A Schaefer; Jan Hillert; Ingrid Kockum; Tomas Olsson; Lars Alfredsson Journal: Eur J Epidemiol Date: 2017-06-08 Impact factor: 8.082