DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Response to interferon beta in multiple sclerosis. The EFO term multiple sclerosis, response to interferon beta was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: multiple sclerosis, response to interferon beta

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

F Clarelli, G Liberatore, M Sorosina, AM Osiceanu, F Esposito, E Mascia, S Santoro, G Pavan, B Colombo, L Moiola, V Martinelli, G Comi, F Martinelli-Boneschi

TITLE:

Pharmacogenetic study of long-term response to interferon-β treatment in multiple sclerosis.

JOURNAL:

The pharmacogenomics journal Jan 2017, Vol 17, pp. 84-91

ABSTRACT:

The aim of the study is the identification of genetic factors that influence the long-term response to interferon-β (IFNβ) (4-year follow-up). We performed a genome-wide association study in 337 IFNβ-treated Italian multiple sclerosis patients at the extreme of treatment response, and we meta-analyzed association effects, integrating results with pathway analysis, gene-expression profiling of IFNβ-stimulated peripheral blood mononuclear cells from 20 healthy controls (HC) and expression quantitative locus (eQTL) analyses. From meta-analysis, 43 markers were associated at P<10(-4), and two of them (rs7298096 and rs4726460) pointed to two genes, NINJ2 and TBXAS1, that were significantly downregulated after IFNβ stimulation in HC (P=3.1 × 10(-9) and 5.6 × 10(-10)). We also observed an eQTL effect for the allele associated with favorable treatment response (rs4726460A); moreover, TBXAS1 appeared downregulated upon IFNβ administration (β=-0.39; P=0.02). Finally, we found an enrichment of pathways related to inflammatory processes and presynaptic membrane, the latter with involvement of genes related to glutamatergic system (GRM3 and GRIK2), confirming its potential role in the response to IFNβ. PUBMED: 26644207
Find other GeneSets from this publication