title: Genetic Variants and Multiple Sclerosis Risk Gene SLC9A9 Expression in Distinct Human Brain Regions.
abstract: A recent genome-wide association study reported a significant association between rs9828519 (G) and nonresponsiveness to interferon-beta (IFN-β) treatment and dysregulation of SLC9A9 expression in multiple sclerosis (MS) cases. We hypothesize that disease-relevant tissues are necessary to detect the effects of rs9828519-tagged SNPs on SLC9A9 expression. Here, we investigated whether SLC9A9 expression is regulated by rs9828519-tagged SNPs in human brain tissue. We used HaploReg to identify the proxy SNPs of the rs9828519 variant based on linkage disequilibrium information from the 1000 Genomes Project. We evaluated the potential association between these SNPs and SLC9A9 expression using multiple expression quantitative trait loci datasets including 10 brain regions of 134 individuals from Braineac, 2 brain regions of 773 samples from brain expression GWAS datasets, and 12 brain regions from the GTEx. We discovered differential SLC9A9 expression in different brain regions and identified 15 rs9828519-tagged SNPs that significantly regulated SLC9A9 expression only in occipital cortex, intralobular white matter, and substantia nigra. Our results advance the understanding of the involvement of SLC9A9 and rs9828519 mechanisms in MS.
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.|School of Life Science and Technology, Harbin Institute of Technology, Room 415, Building 2E, Science Park, Yikuang Street, Nangang District, Harbin, 150080, China.
authors.forename: Guiyou
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Room 415, Building 2E, Science Park, Yikuang Street, Nangang District, Harbin, 150080, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yongshuai
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Neurology, Tianjin HuanHu Hospital, Tianjin, China.
authors.forename: Shoufeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurology, Tianjin NanKai Hospital, Tianjin, China.
authors.forename: Xiuju
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Room 415, Building 2E, Science Park, Yikuang Street, Nangang District, Harbin, 150080, China. qhjiang@hit.edu.cn.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. hjw@tmu.edu.cn.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
mesh_terms: D001921:Brain / Q000473:pathology / Q000502:physiology*; D030541:Databases, Genetic; D015870:Gene Expression; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C478541:SLC9A9 protein, human; D017923:Sodium-Hydrogen Exchangers
keywords: Genome-wide association study; Multiple sclerosis; SLC9A9; rs9828519