PMID- 25948629
OWN - NLM
STAT- MEDLINE
DCOM- 20160822
LR  - 20151030
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 21
IP  - 13
DP  - 2015 Nov
TI  - Burden of risk variants correlates with phenotype of multiple sclerosis.
PG  - 1670-80
LID - 10.1177/1352458514568174 [doi]
AB  - 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.
CI  - (c) The Author(s), 2015.
FAU - Hilven, Kelly
AU  - Hilven K
AD  - Laboratory for Neuroimmunology, Department of Neurosciences, Experimental 
      Neurology, KU Leuven - University of Leuven, Belgium.
FAU - Patsopoulos, Nikolaos A
AU  - Patsopoulos NA
AD  - Department of Neurology, Brigham & Women's Hospital, USA/Harvard Medical School, 
      USA/Broad Institute, USA.
FAU - Dubois, Benedicte
AU  - Dubois B
AD  - Laboratory for Neuroimmunology, Department of Neurosciences, Experimental 
      Neurology, KU Leuven - University of Leuven, Belgium/Department of Neurology, 
      University Hospitals Leuven, Belgium.
FAU - Goris, An
AU  - Goris A
AD  - Laboratory for Neuroimmunology, Department of Neurosciences, Experimental 
      Neurology, KU Leuven - University of Leuven, Belgium an.goris@med.kuleuven.be.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150506
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Oligoclonal Bands)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Belgium/epidemiology
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Immunoglobulin G/blood/*cerebrospinal fluid
MH  - Male
MH  - Multiple Sclerosis, Chronic Progressive/*epidemiology/*genetics
MH  - Oligoclonal Bands/cerebrospinal fluid/*genetics
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - Recurrence
MH  - Risk Factors
OTO - NOTNLM
OT  - IgG index
OT  - Multiple sclerosis
OT  - disease course
OT  - genetic association
OT  - genetic risk
OT  - oligoclonal bands
OT  - relapse rate
EDAT- 2015/05/08 06:00
MHDA- 2016/08/23 06:00
CRDT- 2015/05/08 06:00
PHST- 2014/08/06 00:00 [received]
PHST- 2014/12/19 00:00 [accepted]
PHST- 2015/05/08 06:00 [entrez]
PHST- 2015/05/08 06:00 [pubmed]
PHST- 2016/08/23 06:00 [medline]
AID - 1352458514568174 [pii]
AID - 10.1177/1352458514568174 [doi]
PST - ppublish
SO  - Mult Scler. 2015 Nov;21(13):1670-80. doi: 10.1177/1352458514568174. Epub 2015 May 
      6.