The effect of single nucleotide polymorphisms from genome wide association studies in multiple sclerosis on gene expression.

Journal article

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. METHODS/PRINCIPAL FINDINGS: 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. DISCUSSION: 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.

Authors: Handel, A; Handunnetthi, L; Berlanga, A; Watson, C; Morahan, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PloS one
• Volume: 5
• Issue: 4
• Pages: e10142
• Publication date: 2010-01-01
• DOI: 10.1371/journal.pone.0010142
• EISSN: 1932-6203
• ISSN: 1932-6203
• Language: English
• Keywords: Humans; Genetic Predisposition to Disease; Multiple Sclerosis; Computational Biology; RNA, Messenger; Databases, Nucleic Acid; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Gene Expression