Genome-wide association study and identification of chromosomal enhancer maps in multiple brain regions related to autism spectrum disorder / L. ZHANG in Autism Research, 12-1 (January 2019)  

Public ISBD [article]  inAutism Research > 12-1 (January 2019) . - p.26-32 Titre : Genome-wide association study and identification of chromosomal enhancer maps in multiple brain regions related to autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : L. ZHANG, Auteur ; L. LIU, Auteur ; Y. WEN, Auteur ; M. MA, Auteur ; S. CHENG, Auteur ; J. YANG, Auteur ; P. LI, Auteur ; B. CHENG, Auteur ; Y. DU, Auteur ; X. LIANG, Auteur ; Y. ZHAO, Auteur ; M. DING, Auteur ; X. GUO, Auteur ; F. ZHANG, Auteur Article en page(s) : p.26-32 Langues : Anglais (eng) Mots-clés : autism  biological pathways  brain regions  enhancer Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a complex developmental disorder with strong genetic components involved. Recent studies have demonstrated the importance of non-coding regulatory variants for complex diseases. To explore the roles of chromosomal enhancer regions in the pathogenesis of ASD, we conducted an integrative analysis of genome-wide association study (GWAS) and brain region related enhancer-gene networks for ASD. The GWAS data of ASD were driven from a published study, involving 7,387 ASD cases and 8,567 controls. The enhancer-gene networks of eight brain regions were used here. The GWAS of ASD was first merged respectively with the enhancer datasets of eight brain regions. Pathway enrichment analysis was then performed to detect ASD associated pathways based on the enhancer-related single nucleotide polymorphism (SNPs) of each brain region. We detected multiple genes with brain region specific or common association signals, such as PGM3 (P value = 1.93 x 10(-5) ) and RWDD2A (P value = 1.93 x 10(-5) ) for hippocampus middle, and ENPP4 (all P values <0.05), and ENPP5 (all P values <0.05) for seven brain regions. By comparing the pathway enrichment analysis results of various brain regions, several cross brain regions pathways were detected for ASD, such as REACTOME_POTASSIUM_CHANNELS (all P values <0.05) for six brain regions and KEGG_CELL_ADHESION_MOLECULES_CAMS (all P values <0.05) for seven brain regions. In addition, several pathways were also identified for specific brain regions, such as REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING (P value = 4.00 x 10(-3) ) for angular gyrus, REACTOME_SIGNALING_BY_CONSTITUTIVELY_ACTIVE_EGFR (P value = 2.22 x 10(-3) ) for anterior caudate, and KEGG_PRION_DISEASES (P value = 1.00 x 10(-4) ) for germinal matrix. Our results provide novel clues for understanding the genetic basis of ASD. Autism Research 2019, 12: 26-32. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ASD is a complex developmental disorder with strong genetic components, but the pathogenesis of ASD is still unclear. Using the latest GWAS data and enhancer map, we explored the brain region related biological pathways associated with ASD. Our results provide novel clues for revealing the functional relevance of enhancer variants with ASD and understanding the genetic basis of ASD. En ligne : http://dx.doi.org/10.1002/aur.2001 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=376 [article] Genome-wide association study and identification of chromosomal enhancer maps in multiple brain regions related to autism spectrum disorder [Texte imprimé et/ou numérique] / L. ZHANG, Auteur ; L. LIU, Auteur ; Y. WEN, Auteur ; M. MA, Auteur ; S. CHENG, Auteur ; J. YANG, Auteur ; P. LI, Auteur ; B. CHENG, Auteur ; Y. DU, Auteur ; X. LIANG, Auteur ; Y. ZHAO, Auteur ; M. DING, Auteur ; X. GUO, Auteur ; F. ZHANG, Auteur . - p.26-32. Langues : Anglais (eng) in Autism Research > 12-1 (January 2019) . - p.26-32 Mots-clés : autism  biological pathways  brain regions  enhancer Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a complex developmental disorder with strong genetic components involved. Recent studies have demonstrated the importance of non-coding regulatory variants for complex diseases. To explore the roles of chromosomal enhancer regions in the pathogenesis of ASD, we conducted an integrative analysis of genome-wide association study (GWAS) and brain region related enhancer-gene networks for ASD. The GWAS data of ASD were driven from a published study, involving 7,387 ASD cases and 8,567 controls. The enhancer-gene networks of eight brain regions were used here. The GWAS of ASD was first merged respectively with the enhancer datasets of eight brain regions. Pathway enrichment analysis was then performed to detect ASD associated pathways based on the enhancer-related single nucleotide polymorphism (SNPs) of each brain region. We detected multiple genes with brain region specific or common association signals, such as PGM3 (P value = 1.93 x 10(-5) ) and RWDD2A (P value = 1.93 x 10(-5) ) for hippocampus middle, and ENPP4 (all P values <0.05), and ENPP5 (all P values <0.05) for seven brain regions. By comparing the pathway enrichment analysis results of various brain regions, several cross brain regions pathways were detected for ASD, such as REACTOME_POTASSIUM_CHANNELS (all P values <0.05) for six brain regions and KEGG_CELL_ADHESION_MOLECULES_CAMS (all P values <0.05) for seven brain regions. In addition, several pathways were also identified for specific brain regions, such as REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING (P value = 4.00 x 10(-3) ) for angular gyrus, REACTOME_SIGNALING_BY_CONSTITUTIVELY_ACTIVE_EGFR (P value = 2.22 x 10(-3) ) for anterior caudate, and KEGG_PRION_DISEASES (P value = 1.00 x 10(-4) ) for germinal matrix. Our results provide novel clues for understanding the genetic basis of ASD. Autism Research 2019, 12: 26-32. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ASD is a complex developmental disorder with strong genetic components, but the pathogenesis of ASD is still unclear. Using the latest GWAS data and enhancer map, we explored the brain region related biological pathways associated with ASD. Our results provide novel clues for revealing the functional relevance of enhancer variants with ASD and understanding the genetic basis of ASD. En ligne : http://dx.doi.org/10.1002/aur.2001 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=376

Integrative analysis of transcriptome-wide association study and mRNA expression profiles identifies candidate genes associated with autism spectrum disorders / H. HUANG in Autism Research, 12-1 (January 2019)  

Public ISBD [article]  inAutism Research > 12-1 (January 2019) . - p.33-38 Titre : Integrative analysis of transcriptome-wide association study and mRNA expression profiles identifies candidate genes associated with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : H. HUANG, Auteur ; S. CHENG, Auteur ; M. DING, Auteur ; Y. WEN, Auteur ; M. MA, Auteur ; L. ZHANG, Auteur ; P. LI, Auteur ; B. CHENG, Auteur ; X. LIANG, Auteur ; L. LIU, Auteur ; Y. DU, Auteur ; Y. ZHAO, Auteur ; O. P. KAFLE, Auteur ; B. HAN, Auteur ; F. ZHANG, Auteur Article en page(s) : p.33-38 Langues : Anglais (eng) Mots-clés : autism spectrum disorders  gene set enrichment analysis  mRNA expression profiles  transcriptome-wide association study Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are a group of highly heritable psychiatric syndromes with high prevalence. The genetic mechanism of ASD remains elusive now. Here we conducted a transcriptome-wide association study (TWAS) of ASD. The GWAS summary data of ASD was driven from the Psychiatric Genomics Consortium (PGC) portal, totally involving 5,305 ASD cases and 5,305 controls. FUSION software was applied to the GWAS summary data for tissue-related TWAS of ASD considering brain and blood. The ASD associated genes identified by TWAS were further validated by mRNA expression profiling of ASD and the Simons Foundation for Autism Research (SFARI) Gene tool. DAVID 6.8 was used to perform gene ontology (GO) enrichment analysis of ASD associated genes identified by TWAS. TWAS identified 85 genes with TWAS P value <0.05 for ASD. Further comparing the 85 genes with the differentially expressed genes identified by mRNA expression profiling of ASD patients found 5 overlapped genes, including MUTYH (PTWAS = 0.0460, PmRNA = 0.0040), ARHGAP27 (PTWAS = 0.0100, PmRNA = 0.0016), GCA (PTWAS = 0.0480, PmRNA = 0.0063), CCDC14 (PTWAS = 0.0067, PmRNA = 0.0035), and MED15 (PTWAS = 0.0324, PmRNA = 0.0092). Gene Ontology (GO) enrichment analysis of the genes identified by TWAS detected 10 significant GO terms, such as mitochondrion (P = 0.0051), NAD or NADH binding (P = 0.0169), mitochondrial part (P = 0.0386) and 2-oxoglutarate metabolic process (P = 0.0399). In conclusion, this study identified multiple ASD associated genes and gene sets, providing novel clues for revealing the pathogenesis of ASD. Autism Research 2019, 12: 33-38. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Recent genetic studies of autism spectrum disorders (ASD) have found multiple ASD related genes. However, the results of these studies were hardly replicated with each other, providing limited clues for exploring the genetic mechanism of ASD. This study detected a group of candidate genes showing transcriptome-wide associations with ASD. These results may provide novel clues for revealing the pathogenesis of ASD. En ligne : http://dx.doi.org/10.1002/aur.2048 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=376 [article] Integrative analysis of transcriptome-wide association study and mRNA expression profiles identifies candidate genes associated with autism spectrum disorders [Texte imprimé et/ou numérique] / H. HUANG, Auteur ; S. CHENG, Auteur ; M. DING, Auteur ; Y. WEN, Auteur ; M. MA, Auteur ; L. ZHANG, Auteur ; P. LI, Auteur ; B. CHENG, Auteur ; X. LIANG, Auteur ; L. LIU, Auteur ; Y. DU, Auteur ; Y. ZHAO, Auteur ; O. P. KAFLE, Auteur ; B. HAN, Auteur ; F. ZHANG, Auteur . - p.33-38. Langues : Anglais (eng) in Autism Research > 12-1 (January 2019) . - p.33-38 Mots-clés : autism spectrum disorders  gene set enrichment analysis  mRNA expression profiles  transcriptome-wide association study Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are a group of highly heritable psychiatric syndromes with high prevalence. The genetic mechanism of ASD remains elusive now. Here we conducted a transcriptome-wide association study (TWAS) of ASD. The GWAS summary data of ASD was driven from the Psychiatric Genomics Consortium (PGC) portal, totally involving 5,305 ASD cases and 5,305 controls. FUSION software was applied to the GWAS summary data for tissue-related TWAS of ASD considering brain and blood. The ASD associated genes identified by TWAS were further validated by mRNA expression profiling of ASD and the Simons Foundation for Autism Research (SFARI) Gene tool. DAVID 6.8 was used to perform gene ontology (GO) enrichment analysis of ASD associated genes identified by TWAS. TWAS identified 85 genes with TWAS P value <0.05 for ASD. Further comparing the 85 genes with the differentially expressed genes identified by mRNA expression profiling of ASD patients found 5 overlapped genes, including MUTYH (PTWAS = 0.0460, PmRNA = 0.0040), ARHGAP27 (PTWAS = 0.0100, PmRNA = 0.0016), GCA (PTWAS = 0.0480, PmRNA = 0.0063), CCDC14 (PTWAS = 0.0067, PmRNA = 0.0035), and MED15 (PTWAS = 0.0324, PmRNA = 0.0092). Gene Ontology (GO) enrichment analysis of the genes identified by TWAS detected 10 significant GO terms, such as mitochondrion (P = 0.0051), NAD or NADH binding (P = 0.0169), mitochondrial part (P = 0.0386) and 2-oxoglutarate metabolic process (P = 0.0399). In conclusion, this study identified multiple ASD associated genes and gene sets, providing novel clues for revealing the pathogenesis of ASD. Autism Research 2019, 12: 33-38. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Recent genetic studies of autism spectrum disorders (ASD) have found multiple ASD related genes. However, the results of these studies were hardly replicated with each other, providing limited clues for exploring the genetic mechanism of ASD. This study detected a group of candidate genes showing transcriptome-wide associations with ASD. These results may provide novel clues for revealing the pathogenesis of ASD. En ligne : http://dx.doi.org/10.1002/aur.2048 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=376

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