Target Genes of Autism Risk Loci in Brain Frontal Cortex
Autism spectrum disorder (ASD) is a complex neuropsychiatric disorder. A number of genetic risk loci have been identified for ASD from genome-wide association studies (GWAS); however, their target genes in relevant tissues and cell types remain to be investigated. The frontal cortex is a key region...
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doaj-f53df80c8df04ae098ac6aaccf3d3a002020-11-25T02:40:40ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-08-011010.3389/fgene.2019.00707430084Target Genes of Autism Risk Loci in Brain Frontal CortexYan Sun0Xueming Yao1Michael E. March2Xinyi Meng3Junyi Li4Zhi Wei5Patrick M.A. Sleiman6Patrick M.A. Sleiman7Patrick M.A. Sleiman8Hakon Hakonarson9Hakon Hakonarson10Hakon Hakonarson11Qianghua Xia12Jin Li13Department of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaDepartment of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaCenter for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaDepartment of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaCollege of Computing Sciences, New Jersey Institute of Technology, University Heights, Newark, NJ, United StatesCenter for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, PA, United StatesCenter for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, PA, United StatesDepartment of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaDepartment of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaAutism spectrum disorder (ASD) is a complex neuropsychiatric disorder. A number of genetic risk loci have been identified for ASD from genome-wide association studies (GWAS); however, their target genes in relevant tissues and cell types remain to be investigated. The frontal cortex is a key region in the human brain for communication and cognitive function. To identify risk genes contributing to potential dysfunction in the frontal cortex of ASD patients, we took an in silico approach integrating multi-omics data. We first found genes with expression in frontal cortex tissue that correlates with ASD risk loci by leveraging expression quantitative trait loci (eQTLs) information. Among these genes, we then identified 76 genes showing significant differential expression in the frontal cortex between ASD cases and controls in microarray datasets and further replicated four genes with RNA-seq data. Among the ASD GWAS single nucleotide polymorphisms (SNPs) correlating with the 76 genes, 20 overlap with histone marks and 40 are associated with gene methylation level. Thus, through multi-omics data analyses, we identified genes that may work as target genes of ASD risk loci in the brain frontal cortex.https://www.frontiersin.org/article/10.3389/fgene.2019.00707/fullautismbrain frontal cortexDNA methylationeQTLGWAS locihistone modification |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yan Sun Xueming Yao Michael E. March Xinyi Meng Junyi Li Zhi Wei Patrick M.A. Sleiman Patrick M.A. Sleiman Patrick M.A. Sleiman Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Qianghua Xia Jin Li |
spellingShingle |
Yan Sun Xueming Yao Michael E. March Xinyi Meng Junyi Li Zhi Wei Patrick M.A. Sleiman Patrick M.A. Sleiman Patrick M.A. Sleiman Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Qianghua Xia Jin Li Target Genes of Autism Risk Loci in Brain Frontal Cortex Frontiers in Genetics autism brain frontal cortex DNA methylation eQTL GWAS loci histone modification |
author_facet |
Yan Sun Xueming Yao Michael E. March Xinyi Meng Junyi Li Zhi Wei Patrick M.A. Sleiman Patrick M.A. Sleiman Patrick M.A. Sleiman Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Qianghua Xia Jin Li |
author_sort |
Yan Sun |
title |
Target Genes of Autism Risk Loci in Brain Frontal Cortex |
title_short |
Target Genes of Autism Risk Loci in Brain Frontal Cortex |
title_full |
Target Genes of Autism Risk Loci in Brain Frontal Cortex |
title_fullStr |
Target Genes of Autism Risk Loci in Brain Frontal Cortex |
title_full_unstemmed |
Target Genes of Autism Risk Loci in Brain Frontal Cortex |
title_sort |
target genes of autism risk loci in brain frontal cortex |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2019-08-01 |
description |
Autism spectrum disorder (ASD) is a complex neuropsychiatric disorder. A number of genetic risk loci have been identified for ASD from genome-wide association studies (GWAS); however, their target genes in relevant tissues and cell types remain to be investigated. The frontal cortex is a key region in the human brain for communication and cognitive function. To identify risk genes contributing to potential dysfunction in the frontal cortex of ASD patients, we took an in silico approach integrating multi-omics data. We first found genes with expression in frontal cortex tissue that correlates with ASD risk loci by leveraging expression quantitative trait loci (eQTLs) information. Among these genes, we then identified 76 genes showing significant differential expression in the frontal cortex between ASD cases and controls in microarray datasets and further replicated four genes with RNA-seq data. Among the ASD GWAS single nucleotide polymorphisms (SNPs) correlating with the 76 genes, 20 overlap with histone marks and 40 are associated with gene methylation level. Thus, through multi-omics data analyses, we identified genes that may work as target genes of ASD risk loci in the brain frontal cortex. |
topic |
autism brain frontal cortex DNA methylation eQTL GWAS loci histone modification |
url |
https://www.frontiersin.org/article/10.3389/fgene.2019.00707/full |
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