Association and gene–gene interactions study of reelin signaling pathway related genes with autism in the Han Chinese population / Yidong SHEN in Autism Research, 9-4 (April 2016)  

Public ISBD [article]  inAutism Research > 9-4 (April 2016) . - p.436-442 Titre : Association and gene–gene interactions study of reelin signaling pathway related genes with autism in the Han Chinese population Type de document : Texte imprimé et/ou numérique Auteurs : Yidong SHEN, Auteur ; Guanglei XUN, Auteur ; Hui GUO, Auteur ; Yiqun HE, Auteur ; Jianjun OU, Auteur ; Huixi DONG, Auteur ; Kun XIA, Auteur ; Jingping ZHAO, Auteur Article en page(s) : p.436-442 Langues : Anglais (eng) Mots-clés : autism  reelin  signaling pathway  interaction  polymorphism Index. décimale : PER Périodiques Résumé : Autism is a neurodevelopmental disorder with unclear etiology. Reelin had been proposed to participate in the etiology of autism due to its important role in brain development. The goal of this study was to explore the association and gene–gene interactions of reelin signaling pathway related genes (RELN, VLDLR, LRP8, DAB1, FYN, and CDK5) with autism in Han Chinese population. Genotyping data of the six genes were obtained from a recent genome-wide association study performed in 430 autistic children who fulfilled the DSM-IV-TR criteria for autistic disorder, and 1,074 healthy controls. Single marker case-control association analysis and haplotype case-control association analysis were conducted after the data was screened. Multifactor dimensionality reduction (MDR) was applied to further test gene–gene interactions. Neither the single marker nor the haplotype association tests found any significant difference between the autistic group and the control group after permutation test of 1,000 rounds. The 4-locus MDR model (comprising rs6143734, rs1858782, rs634500, and rs1924267 which belong to RELN and DAB1) was determined to be the model with the highest cross-validation consistency (CVC) and testing balanced accuracy. The results indicate that an interaction between RELN and DAB1 may increase the risk of autism in the Han Chinese population. Furthermore, it can also be inferred that the involvement of RELN in the etiology of autism would occur through interaction with DAB1. Autism Res 2016, 9: 436–442. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1540 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=287 [article] Association and gene–gene interactions study of reelin signaling pathway related genes with autism in the Han Chinese population [Texte imprimé et/ou numérique] / Yidong SHEN, Auteur ; Guanglei XUN, Auteur ; Hui GUO, Auteur ; Yiqun HE, Auteur ; Jianjun OU, Auteur ; Huixi DONG, Auteur ; Kun XIA, Auteur ; Jingping ZHAO, Auteur . - p.436-442. Langues : Anglais (eng) in Autism Research > 9-4 (April 2016) . - p.436-442 Mots-clés : autism  reelin  signaling pathway  interaction  polymorphism Index. décimale : PER Périodiques Résumé : Autism is a neurodevelopmental disorder with unclear etiology. Reelin had been proposed to participate in the etiology of autism due to its important role in brain development. The goal of this study was to explore the association and gene–gene interactions of reelin signaling pathway related genes (RELN, VLDLR, LRP8, DAB1, FYN, and CDK5) with autism in Han Chinese population. Genotyping data of the six genes were obtained from a recent genome-wide association study performed in 430 autistic children who fulfilled the DSM-IV-TR criteria for autistic disorder, and 1,074 healthy controls. Single marker case-control association analysis and haplotype case-control association analysis were conducted after the data was screened. Multifactor dimensionality reduction (MDR) was applied to further test gene–gene interactions. Neither the single marker nor the haplotype association tests found any significant difference between the autistic group and the control group after permutation test of 1,000 rounds. The 4-locus MDR model (comprising rs6143734, rs1858782, rs634500, and rs1924267 which belong to RELN and DAB1) was determined to be the model with the highest cross-validation consistency (CVC) and testing balanced accuracy. The results indicate that an interaction between RELN and DAB1 may increase the risk of autism in the Han Chinese population. Furthermore, it can also be inferred that the involvement of RELN in the etiology of autism would occur through interaction with DAB1. Autism Res 2016, 9: 436–442. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1540 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=287

Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder / Lin WANG in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 75 p. Titre : Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Lin WANG, Auteur ; Yi ZHANG, Auteur ; Kuokuo LI, Auteur ; Zheng WANG, Auteur ; Xiaomeng WANG, Auteur ; Bin LI, Auteur ; Guihu ZHAO, Auteur ; Zhenghuan FANG, Auteur ; Zhengbao LING, Auteur ; Tengfei LUO, Auteur ; Lu XIA, Auteur ; Yanping LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Jinchen LI, Auteur ; Zhongsheng SUN, Auteur ; Kun XIA, Auteur Article en page(s) : 75 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  De novo variant  Expression pattern  Functional network  Recessive inherited variant Index. décimale : PER Périodiques Résumé : BACKGROUND: Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs). METHODS: We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns. RESULTS: Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p?=?0.038) and X-linked inherited PTVs in males (p?=?0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs. LIMITATIONS: The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD. CONCLUSIONS: ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs. En ligne : http://dx.doi.org/10.1186/s13229-020-00382-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433 [article] Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder [Texte imprimé et/ou numérique] / Lin WANG, Auteur ; Yi ZHANG, Auteur ; Kuokuo LI, Auteur ; Zheng WANG, Auteur ; Xiaomeng WANG, Auteur ; Bin LI, Auteur ; Guihu ZHAO, Auteur ; Zhenghuan FANG, Auteur ; Zhengbao LING, Auteur ; Tengfei LUO, Auteur ; Lu XIA, Auteur ; Yanping LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Jinchen LI, Auteur ; Zhongsheng SUN, Auteur ; Kun XIA, Auteur . - 75 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 75 p. Mots-clés : Autism spectrum disorder  De novo variant  Expression pattern  Functional network  Recessive inherited variant Index. décimale : PER Périodiques Résumé : BACKGROUND: Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs). METHODS: We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns. RESULTS: Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p?=?0.038) and X-linked inherited PTVs in males (p?=?0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs. LIMITATIONS: The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD. CONCLUSIONS: ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs. En ligne : http://dx.doi.org/10.1186/s13229-020-00382-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433

Genome-wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders / Lu XIA in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.382-396 Titre : Genome-wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders Type de document : Texte imprimé et/ou numérique Auteurs : Lu XIA, Auteur ; Jianjun OU, Auteur ; Kuokuo LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Ting BAI, Auteur ; Jingping ZHAO, Auteur ; Kun XIA, Auteur ; Fengyu ZHANG, Auteur Article en page(s) : p.382-396 Langues : Anglais (eng) Mots-clés : autism  genome-wide association study  neuropsychiatric disorders  transmission disequilibrium test Index. décimale : PER Périodiques Résumé : Autism is a common neurodevelopmental disorder with a moderate to a high degree of heritability, but only a few common genetic variants that explain the heritability have been associated. We performed a genome-wide transmission disequilibrium test analysis of a newly genotyped autism case-parent triad samples (127 trios) in Han Chinese, identified top association signals at multiple single nucleotide polymorphisms (SNPs), including rs9839376 (OR = 2.59, P = 1.27 x 10(-05) ) at KCNMB2, rs6044680 (OR = 0.319, P = 4.82 x 10(-05) ) and rs7274133 (OR = 0.313, P = 3.22 x 10(-05) ) at PCSK2, and rs310619 (OR = 2.40, P = 7.44 x 10(-05) ) at EEF1A2. Furthermore, a genome-wide combined P-value of individual SNPs in two independent case-parent triad samples (total 402 triads, n = 1,206) identified SNPs at EGFLAM, ZDHHC2, AGBL1, and SNX29 as additional association signals for autism. While none of these signals achieved a genome-wide significance in the two samples of our study, they have been reported in a previous genome-wide association study of neuropsychiatric disorders, and the majority of these SNP have a significant cis-regulatory association with mRNA in human tissues (false discovery rate (FDR) < 0.05). Our study warrants further study or replication with additional sample for association with autism and other neuropsychiatric disorders. Autism Res 2020, 13: 382-396. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism is a common neurodevelopmental disorder, heritable, but only a few common genetic variants that explain the heritability have been associated. We conducted a genome-wide association study with two cohorts of autism case-parent triad samples in Han Chinese and identified multiple single nucleotide polymorphisms that were reported as strong association signals in a previous genome-wide association study of other neuropsychiatric disorders or related traits. Our study provides evidence for shared genetic variants among autism and other neuropsychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2229 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Genome-wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders [Texte imprimé et/ou numérique] / Lu XIA, Auteur ; Jianjun OU, Auteur ; Kuokuo LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Ting BAI, Auteur ; Jingping ZHAO, Auteur ; Kun XIA, Auteur ; Fengyu ZHANG, Auteur . - p.382-396. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.382-396 Mots-clés : autism  genome-wide association study  neuropsychiatric disorders  transmission disequilibrium test Index. décimale : PER Périodiques Résumé : Autism is a common neurodevelopmental disorder with a moderate to a high degree of heritability, but only a few common genetic variants that explain the heritability have been associated. We performed a genome-wide transmission disequilibrium test analysis of a newly genotyped autism case-parent triad samples (127 trios) in Han Chinese, identified top association signals at multiple single nucleotide polymorphisms (SNPs), including rs9839376 (OR = 2.59, P = 1.27 x 10(-05) ) at KCNMB2, rs6044680 (OR = 0.319, P = 4.82 x 10(-05) ) and rs7274133 (OR = 0.313, P = 3.22 x 10(-05) ) at PCSK2, and rs310619 (OR = 2.40, P = 7.44 x 10(-05) ) at EEF1A2. Furthermore, a genome-wide combined P-value of individual SNPs in two independent case-parent triad samples (total 402 triads, n = 1,206) identified SNPs at EGFLAM, ZDHHC2, AGBL1, and SNX29 as additional association signals for autism. While none of these signals achieved a genome-wide significance in the two samples of our study, they have been reported in a previous genome-wide association study of neuropsychiatric disorders, and the majority of these SNP have a significant cis-regulatory association with mRNA in human tissues (false discovery rate (FDR) < 0.05). Our study warrants further study or replication with additional sample for association with autism and other neuropsychiatric disorders. Autism Res 2020, 13: 382-396. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism is a common neurodevelopmental disorder, heritable, but only a few common genetic variants that explain the heritability have been associated. We conducted a genome-wide association study with two cohorts of autism case-parent triad samples in Han Chinese and identified multiple single nucleotide polymorphisms that were reported as strong association signals in a previous genome-wide association study of other neuropsychiatric disorders or related traits. Our study provides evidence for shared genetic variants among autism and other neuropsychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2229 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

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