title: Burden of risk variants correlates with phenotype of multiple sclerosis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory for Neuroimmunology, Department of Neurosciences, Experimental Neurology, KU Leuven - University of Leuven, Belgium.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hilven
authors.affiliation: Department of Neurology, Brigham & Women's Hospital, USA/Harvard Medical School, USA/Broad Institute, USA.
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Patsopoulos
authors.affiliation: Laboratory for Neuroimmunology, Department of Neurosciences, Experimental Neurology, KU Leuven - University of Leuven, Belgium/Department of Neurology, University Hospitals Leuven, Belgium.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dubois
authors.affiliation: Laboratory for Neuroimmunology, Department of Neurosciences, Experimental Neurology, KU Leuven - University of Leuven, Belgium an.goris@med.kuleuven.be.
authors.forename: An
authors.initials: A
authors.lastname: Goris
mesh_terms: D000328:Adult; D000483:Alleles; D001530:Belgium / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000453:epidemiology* / Q000235:genetics*; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012307:Risk Factors
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D043025:Oligoclonal Bands
keywords: IgG index; Multiple sclerosis; disease course; genetic association; genetic risk; oligoclonal bands; relapse rate