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Genetic dissection of glutathione S-transferase omega-1:identification of novel downstream targets and Alzheimer's disease pathways

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Neural Regeneration Research 2022年第11期17卷 2452-2458页

作者： Yue Jia Meng-Die Gao Yun-Fang Liu Lu Lu Gang Chen Ying Chen Department of Histology and Embryology Medical CollegeNantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Genetics Genomics and InformaticsUniversity of Tennessee Health Science CenterMemphisTNUSA Department of Anesthesiology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Alzheimer's disease(AD)is affected by genetic factors.Polymorphisms in the glutathione S-transfe rase omega-1(Gsto1)gene have been shown by genetic correlation analyses performed in different ethnic populations to be genetic risk factors for AD.Gene expression profile data from BXD recombinant inbred mice were used in combination with genetic and bioinformatic analyses to chara cterize the mechanisms underlying regulation of Gstol variation regulation and to identify network membe rs that may contribute to AD risk or progression.Allele-specific assays confirmed that variation in Gstol expression is controlled by cis-expression quantitative trait loci.We found that Gstol mRNA levels were related to several central nervous system traits,such as glial acidic fibrillary protein levels in the caudate putamen,co rtical gray matter volume,and hippocampus mossy fiber pathway volume.We identified 2168 genes whose expression was highly correlated with that of Gsto1.Some genes were enriched for the most common neurodegenerative diseases.Some Gsto1-related genes identified in this study had previously been identified as susceptibility genes for AD,such as APP,Grin2 b,Ide,and Psenen.To evaluate the relationships between Gstol and candidate network members,we transfected astrocytes with Gstol siRNA and assessed the effect on putative downstream effecto rs.We confirmed that knockdown of Gstol had a significant influence on Pa2g4 expression,suggesting that Pa2g4 may be a downstream effector of Gstol,and that both genes intera ct with other genes in a network during AD pathogenesis.

关键词： Alzheimer's disease BXD recombinant inbred mice co-expression correlation analysis expression quantitative trait locus expression variation genetic dissection glutathione S-transferase omega-1 hippocampus proliferation-associated 2G4

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ezQTL:A Web Platform for Interactive Visualization and Colocalization of QTLs and GWAS Loci

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Genomics, Proteomics & Bioinformatics 2022年第3期20卷 541-548页

作者： Tongwu Zhang Alyssa Klein Jian Sang Jiyeon Choi Kevin M.Brown Division of Cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892USA

Genome-wide association studies(GWAS)have identified thousands of genomic loci associated with complex diseases and traits,including cancer.The vast majority of common traitassociated variants identified via GWAS fall in non-coding regions of the genome,posing a challenge in elucidating the causal variants,genes,and mechanisms involved.expression quantitative trait locus(eQTL)and other molecular QTL studies have been valuable resources in identifying candidate causal genes from GWAS loci through statistical colocalization methods.While QTL colocalization is becoming a standard analysis in post-GWAS investigation,an easy web tool for users to perform formal colocalization analyses with either user-provided or public GWAS and eQTL datasets has been lacking.Here,we present ezQTL,a web-based bioinformatic application to interactively visualize and analyze genetic association data such as GWAS loci and molecular QTLs under different linkage disequilibrium(LD)patterns(1000 Genomes Project,UK Biobank,or user-provided data).This application allows users to perform data quality control for variants matched between different datasets,LD visualization,and two-trait colocalization analyses using two state-of-the-art methodologies(eCAVIAR and HyPrColoc),including batch processing.ezQTL is a free and publicly available cross-platform web tool,which can be accessed online at https://analysistools.***.gov/ezqtl.

关键词： Genome-wide association study expression quantitative trait locus Colocalization Linkage disequilibrium Visualization

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