Genotype-phenotype correlation for non-HLA disease associated risk alleles in multiple sclerosis.
BACKGROUND
Recent advances in MS genetics have led to the successful identification of a number of novel disease associated non-HLA genes. It is now becoming possible to begin to analyse the possible effects of these genes on aspects of disease phenotype where longitudinal clinical data is available.


OBJECTIVE
We examined phenotypic impact of 10 non-HLA disease associated single nucleotide polymorphisms (SNPs) in 1003 patients with MS followed for an average of 14.1 years.


METHODS
Association of SNPs with time to established disability milestones (Expanded Disability Status Scale (EDSS) 4.0, 6.0, 8.0), onset of secondary progression and cross-sectional aspects of early phenotype were tested using survival analysis.


RESULTS
No SNP was associated with systematic deflection in time to disability milestones, age at onset or time to secondary progression.


CONCLUSIONS
Genotypic information from non-HLA associated SNPs is unlikely to inform individual patient prognosis in the clinical setting although minor phenotypic effects operative at specific phases of disease cannot be excluded. This preliminary study provides a framework for future genotype-phenotype analysis in MS and will need to be replicated in independent patient cohorts.
Department of Psychological Medicine and Neurology, Cardiff University, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK.
Katharine
K
Harding
Gillian
G
Ingram
Mark
M
Cossburn
Claire
C
Hirst
Trevor
T
Pickersgill
Yoav
Y
Ben-Shlomo
Neil
N
Robertson
D000328:Adult; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
D006680:HLA Antigens