Guiyou Liu1, Fang Zhang2, Yongshuai Jiang3, Yang Hu1, Zhongying Gong4, Shoufeng Liu5, Xiuju Chen6, Qinghua Jiang1, Junwei Hao2. 1. School of Life Science and Technology, Harbin Institute of Technology, Harbin, China. 2. Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China. 3. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. 4. Department of Neurology, Tianjin First Central Hospital, Tianjin, China. 5. Department of Neurology, Tianjin HuanHu Hospital, Tianjin, China. 6. Department of Neurology, Tianjin NanKai Hospital, Tianjin, China.
Abstract
BACKGROUND: Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. OBJECTIVE: We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. METHODS: Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. RESULTS: In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. CONCLUSION: We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.
BACKGROUND: Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. OBJECTIVE: We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. METHODS: Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. RESULTS: In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. CONCLUSION: We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.
Authors: M Pazhouhandeh; M-A Sahraian; S D Siadat; A Fateh; F Vaziri; F Tabrizi; F Ajorloo; A K Arshadi; E Fatemi; S Piri Gavgani; F Mahboudi; F Rahimi Jamnani Journal: Clin Exp Immunol Date: 2018-01-25 Impact factor: 4.330