The effect of single nucleotide polymorphisms from genome wide association studies in multiple sclerosis on gene expression.
BACKGROUND
Multiple sclerosis (MS) is a complex neurological disorder. Its aetiology involves both environmental and genetic factors. Recent genome-wide association studies have identified a number of single nucleotide polymorphisms (SNPs) associated with susceptibility to (MS). We investigated whether these genetic variations were associated with alteration in gene expression.


RESULTS
We used a database of mRNA expression and genetic variation derived from immortalised peripheral lymphocytes to investigate polymorphisms associated with MS for correlation with gene expression. Several SNPs were found to be associated with changes in expression: in particular two with HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1, HLA-DRB4 and HLA-DRB5, one with ZFP57, one with CD58, two with IL7 and FAM164A, and one with FAM119B, TSFM and KUB3. We found minimal cross-over with a recent whole genome expression study in MS patients.


CONCLUSIONS
We have shown that many susceptibility loci in MS are associated with changes in gene expression using an unbiased expression database. Several of these findings suggest novel gene candidates underlying the effects of MS-associated genetic variation.
Handel
Adam E
AE
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Handunnetthi
Lahiru
L
Berlanga
Antonio J
AJ
Watson
Corey T
CT
Morahan
Julia M
JM
Ramagopalan
Sreeram V
SV
D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D015870:Gene Expression / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger
D012333:RNA, Messenger
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