scholarly journals Gene-Based Tests of a Genome-Wide Association Study Dataset Highlight Novel Multiple Sclerosis Risk Genes

2021 ◽  
Vol 15 ◽  
Author(s):  
He Li ◽  
Xiaodan Hou ◽  
Yan Liang ◽  
Fang Xu ◽  
Xiyue Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Healthy Controls ◽  
Risk Genes ◽  
Gwas Dataset ◽  
Genome Wide ◽  
A Genome

Multiple sclerosis (MS) is an autoimmune disorder influenced by genetic and environmental factors. Many studies have provided insights into genetic factors’ contribution to MS via large-scale genome-wide association study (GWAS) datasets. However, genetic variants identified to date do not adequately explain genetic risks for MS. This study hypothesized that novel MS risk genes could be identified by analyzing the MS-GWAS dataset using gene-based tests. We analyzed a GWAS dataset consisting of 9,772 MS cases and 17,376 healthy controls of European descent. We performed gene-based tests of 464,357 autosomal single nucleotide polymorphisms (SNPs) using two methods (PLINK and VEGAS2) and identified 28 shared genes satisfied p-value < 4.56 × 10–6. In further gene expression analysis, ten of the 28 genes were significantly differentially expressed in the MS case-control gene expression omnibus (GEO) database. GALC and HLA-DOB showed the most prominent differences in gene expression (two- and three-fold, respectively) between MS patients and healthy controls. In conclusion, our results reveal more information about MS hereditary characteristics and provide a basis for further studies.

scholarly journals A genome-wide association study of brain lesion distribution in multiple sclerosis

Brain ◽  
2013 ◽  
Vol 136 (4) ◽  
pp. 1012-1024 ◽  
Author(s):  
Pierre-Antoine Gourraud ◽  
Michael Sdika ◽  
Pouya Khankhanian ◽  
Roland G. Henry ◽  
Azadeh Beheshtian ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Brain Lesion ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

2010 ◽  
Vol 12 (2) ◽  
pp. 110-115 ◽  
Author(s):  
M L Cavanillas ◽  
O Fernández ◽  
M Comabella ◽  
A Alcina ◽  
M Fedetz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

Cannabis use and schizophrenia: Chicken or egg?

2018 ◽  
Vol 10 (460) ◽  
pp. eaav0342
Author(s):  
Laura C. Andreae
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Cannabis Use ◽  
Genome Wide Association ◽  
Risk Genes ◽  
Genome Wide ◽  
A Genome

A genome-wide association study identifies risk genes for cannabis use and examines direction of causality for its association with schizophrenia.

A genome-wide association study in progressive multiple sclerosis

2012 ◽  
Vol 18 (10) ◽  
pp. 1384-1394 ◽  
Author(s):  
Filippo Martinelli-Boneschi ◽  
Federica Esposito ◽  
Paola Brambilla ◽  
Eva Lindström ◽  
Giovanni Lavorgna ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Axonal Guidance ◽  
Genome Wide Association ◽  
P Value ◽  
Suggestive Evidence ◽  
Genome Wide ◽  
A Genome ◽  
Herv Element

Background: The role played by genetic factors in influencing the clinical course of multiple sclerosis (MS) is not yet well established. Objective: We aimed to identify genetic variants associated with progressive MS (PrMS). Methods: We conducted a genome-wide association study (GWAS) in 197 patients with PrMS and 234 controls of Italian origin. We tested the top 20 single nucleotide polymorphisms (SNPs) with suggestive evidence of association ( p-value<10−4) in two independent sets of primary progressive MS cases and controls. Results: We identified a risk-associated SNP in the HLA region in linkage disequilibrium (LD) with DRB1*1501 and DQB*0602 loci, with genome-wide significance (rs3129934T, pcombined=6.7×10-16, OR=2.34, 95% CI=1.90–2.87), and a novel locus on chromosome 7q35 with suggestive evidence of association (rs996343G, pcombined=2.4×10-5, OR=0.70, 95% CI=0.59–0.83) which maps within a human endogenous retroviral (HERV) element. The new locus did not have a ‘ cis’ effect on RNA expression in lymphoblastic cell lines, but pathway analyses of ‘ trans’ effects point to an expression regulation of genes involved in neurodegeneration, including glutamate metabolism ( p<0.01) and axonal guidance signalling ( p<0.02). Conclusions: We have confirmed the established association with the HLA region and, despite the low statistical power of the study, we found suggestive evidence for association with a novel locus on chromosome 7, with a putative regulatory role.

scholarly journals The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes

2012 ◽  
Vol 21 (9) ◽  
pp. 2111-2123 ◽  
Author(s):  
Darren A. Cusanovich ◽  
Christine Billstrand ◽  
Xiang Zhou ◽  
Claudia Chavarria ◽  
Sherryl De Leon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Candidate Genes ◽  
Gene Expression Data ◽  
Lymphocyte Count ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Expression Data ◽  
Genome Wide ◽  
A Genome

scholarly journals Epigenome-wide association study of narcolepsy-affected lateral hypothalamic brains, and overlapping DNA methylation profiles between narcolepsy and multiple sclerosis

SLEEP ◽  
2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Mihoko Shimada ◽  
Taku Miyagawa ◽  
Akari Takeshima ◽  
Akiyoshi Kakita ◽  
Hiromi Toyoda ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dna Methylation ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Basic Protein ◽  
Temporal Cortex ◽  
Brain Regions ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

Abstract Narcolepsy with cataplexy is a sleep disorder caused by a deficiency in hypocretin neurons in the lateral hypothalamus (LH). Here we performed an epigenome-wide association study (EWAS) of DNA methylation for narcolepsy and replication analyses using DNA samples extracted from two brain regions: LH (Cases: N = 4; Controls: N = 4) and temporal cortex (Cases: N = 7; Controls: N = 7). Seventy-seven differentially methylated regions (DMRs) were identified in the LH analysis, with the top association of a DMR in the myelin basic protein (MBP) region. Only five DMRs were detected in the temporal cortex analysis. Genes annotated to LH DMRs were significantly associated with pathways related to fatty acid response or metabolism. Two additional analyses applying the EWAS data were performed: (1) investigation of methylation profiles shared between narcolepsy and other disorders and (2) an integrative analysis of DNA methylation data and a genome-wide association study for narcolepsy. The results of the two approaches, which included significant overlap of methylated positions associated with narcolepsy and multiple sclerosis, indicated that the two diseases may partly share their pathogenesis. In conclusion, DNA methylation in LH where loss of orexin-producing neurons occurs may play a role in the pathophysiology of the disease.

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