Kelly Hilven1, Nikolaos A Patsopoulos2, Bénédicte Dubois3, An Goris4. 1. Laboratory for Neuroimmunology, Department of Neurosciences, Experimental Neurology, KU Leuven - University of Leuven, Belgium. 2. Department of Neurology, Brigham & Women's Hospital, USA/Harvard Medical School, USA/Broad Institute, USA. 3. Laboratory for Neuroimmunology, Department of Neurosciences, Experimental Neurology, KU Leuven - University of Leuven, Belgium/Department of Neurology, University Hospitals Leuven, Belgium. 4. Laboratory for Neuroimmunology, Department of Neurosciences, Experimental Neurology, KU Leuven - University of Leuven, Belgium an.goris@med.kuleuven.be.
Abstract
BACKGROUND: More than 100 common variants underlying multiple sclerosis (MS) susceptibility have been identified, but their effect on disease phenotype is still largely unknown. OBJECTIVE: The objective of this paper is to assess whether the cumulative genetic risk score of currently known susceptibility variants affects clinical presentation. METHODS: A cumulative genetic risk score was based on four human leukocyte antigen (HLA) and 106 non-HLA risk loci genotyped or imputed in 842 Belgian MS patients and 321 controls. Non-parametric analyses were applied. RESULTS: An increased genetic risk is observed for MS patients, including subsets such as oligoclonal band-negative and primary progressive MS patients, compared to controls. Within the patient group, a stronger association between HLA risk variants and the presence of oligoclonal bands, an increased immunoglobulin G (IgG) index and female gender was apparent. Results suggest an association between a higher accumulation of non-HLA risk variants and increased relapse rate as well as shorter relapse-free intervals after disease onset. CONCLUSION: MS patients display a significantly increased genetic risk compared to controls, irrespective of disease course or presence of oligoclonal bands. Whereas the cumulative burden of non-HLA risk variants appears to be reflected in the relapses of MS patients, the HLA region influences intrathecal IgG levels.
BACKGROUND: More than 100 common variants underlying multiple sclerosis (MS) susceptibility have been identified, but their effect on disease phenotype is still largely unknown. OBJECTIVE: The objective of this paper is to assess whether the cumulative genetic risk score of currently known susceptibility variants affects clinical presentation. METHODS: A cumulative genetic risk score was based on four human leukocyte antigen (HLA) and 106 non-HLA risk loci genotyped or imputed in 842 Belgian MSpatients and 321 controls. Non-parametric analyses were applied. RESULTS: An increased genetic risk is observed for MSpatients, including subsets such as oligoclonal band-negative and primary progressive MSpatients, compared to controls. Within the patient group, a stronger association between HLA risk variants and the presence of oligoclonal bands, an increased immunoglobulin G (IgG) index and female gender was apparent. Results suggest an association between a higher accumulation of non-HLA risk variants and increased relapse rate as well as shorter relapse-free intervals after disease onset. CONCLUSION:MSpatients display a significantly increased genetic risk compared to controls, irrespective of disease course or presence of oligoclonal bands. Whereas the cumulative burden of non-HLA risk variants appears to be reflected in the relapses of MSpatients, the HLA region influences intrathecal IgG levels.
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