Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations / Xiaoxi LIU in Autism Research, 9-3 (March 2016)  

Public ISBD [article]  inAutism Research > 9-3 (March 2016) . - p.340-349 Titre : Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations Type de document : texte imprimé Auteurs : Xiaoxi LIU, Auteur ; Takafumi SHIMADA, Auteur ; Takeshi OTOWA, Auteur ; Yu-Yu WU, Auteur ; Yoshiya KAWAMURA, Auteur ; Mamoru TOCHIGI, Auteur ; Yasuhide IWATA, Auteur ; Tadashi UMEKAGE, Auteur ; Tomoko TOYOTA, Auteur ; Motoko MAEKAWA, Auteur ; Yoshimi IWAYAMA, Auteur ; Katsuaki SUZUKI, Auteur ; Chihiro KAKIUCHI, Auteur ; Hitoshi KUWABARA, Auteur ; Yukiko KANO, Auteur ; Hisami NISHIDA, Auteur ; Toshiro SUGIYAMA, Auteur ; Nobumasa KATO, Auteur ; Chia-Hsiang CHEN, Auteur ; Norio MORI, Auteur ; Kazuo YAMADA, Auteur ; Takeo YOSHIKAWA, Auteur ; Kiyoto KASAI, Auteur ; Katsushi TOKUNAGA, Auteur ; Tsukasa SASAKI, Auteur ; Susan Shur-Fen GAU, Auteur Article en page(s) : p.340-349 Langues : Anglais (eng) Mots-clés : autism  autism spectrum disorder  genome-wide association study  genetics  common variation Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with strong genetic basis. To identify common genetic variations conferring the risk of ASD, we performed a two-stage genome-wide association study using ASD family and healthy control samples obtained from East Asian populations. A total of 166 ASD families (n = 500) and 642 healthy controls from the Japanese population were used as the discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array 6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy controls, as well as 418 Chinese Han trios (n = 1,254), were genotyped by TaqMan platform. Case–control analysis, family based association test, and transmission/disequilibrium test (TDT) were then conducted to test the association. In the discovery stage, significant associations were suggested for 14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and CSMD1. In addition, significant associations were identified for several novel genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a meta-analysis combining the Japanese replication samples, the strongest signal was found at rs16976358 (P = 6.04 × 10−7), which is located near the RIT2 gene. In summary, our results provide independent support to known ASD candidate genes and highlight a number of novel genes warranted to be further investigated in a larger sample set in an effort to improve our understanding of the genetic basis of ASD. Autism Res 2016, 9: 340–349. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1536 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=285 [article] Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations [texte imprimé] / Xiaoxi LIU, Auteur ; Takafumi SHIMADA, Auteur ; Takeshi OTOWA, Auteur ; Yu-Yu WU, Auteur ; Yoshiya KAWAMURA, Auteur ; Mamoru TOCHIGI, Auteur ; Yasuhide IWATA, Auteur ; Tadashi UMEKAGE, Auteur ; Tomoko TOYOTA, Auteur ; Motoko MAEKAWA, Auteur ; Yoshimi IWAYAMA, Auteur ; Katsuaki SUZUKI, Auteur ; Chihiro KAKIUCHI, Auteur ; Hitoshi KUWABARA, Auteur ; Yukiko KANO, Auteur ; Hisami NISHIDA, Auteur ; Toshiro SUGIYAMA, Auteur ; Nobumasa KATO, Auteur ; Chia-Hsiang CHEN, Auteur ; Norio MORI, Auteur ; Kazuo YAMADA, Auteur ; Takeo YOSHIKAWA, Auteur ; Kiyoto KASAI, Auteur ; Katsushi TOKUNAGA, Auteur ; Tsukasa SASAKI, Auteur ; Susan Shur-Fen GAU, Auteur . - p.340-349. Langues : Anglais (eng) in Autism Research > 9-3 (March 2016) . - p.340-349 Mots-clés : autism  autism spectrum disorder  genome-wide association study  genetics  common variation Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with strong genetic basis. To identify common genetic variations conferring the risk of ASD, we performed a two-stage genome-wide association study using ASD family and healthy control samples obtained from East Asian populations. A total of 166 ASD families (n = 500) and 642 healthy controls from the Japanese population were used as the discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array 6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy controls, as well as 418 Chinese Han trios (n = 1,254), were genotyped by TaqMan platform. Case–control analysis, family based association test, and transmission/disequilibrium test (TDT) were then conducted to test the association. In the discovery stage, significant associations were suggested for 14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and CSMD1. In addition, significant associations were identified for several novel genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a meta-analysis combining the Japanese replication samples, the strongest signal was found at rs16976358 (P = 6.04 × 10−7), which is located near the RIT2 gene. In summary, our results provide independent support to known ASD candidate genes and highlight a number of novel genes warranted to be further investigated in a larger sample set in an effort to improve our understanding of the genetic basis of ASD. Autism Res 2016, 9: 340–349. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1536 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=285

Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms / Yasuhiko KATO in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 15 p. Titre : Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms Type de document : texte imprimé Auteurs : Yasuhiko KATO, Auteur ; Hitoshi KUWABARA, Auteur ; Takashi OKADA, Auteur ; Toshio MUNESUE, Auteur ; Seico BENNER, Auteur ; Miho KURODA, Auteur ; Masaki KOJIMA, Auteur ; Walid YASSIN, Auteur ; Yosuke ERIGUCHI, Auteur ; Yosuke KAMENO, Auteur ; Chihiro MURAYAMA, Auteur ; Tomoko NISHIMURA, Auteur ; Kenji TSUCHIYA, Auteur ; Kiyoto KASAI, Auteur ; Norio OZAKI, Auteur ; Hirotaka KOSAKA, Auteur ; Hidenori YAMASUE, Auteur Article en page(s) : 15 p. Langues : Anglais (eng) Mots-clés : Administration, Intranasal  Adolescent  Adult  Autistic Disorder/blood/drug therapy/metabolism/psychology  Double-Blind Method  Facial Expression  Humans  Male  Metabolomics  Middle Aged  Oxytocin/administration & dosage/blood/pharmacokinetics  Sarcosine/analogs & derivatives/blood  Social Behavior  Treatment Outcome  Young Adult  Asperger  Autism  Clinical trial  Developmental disorders  Facial expression  N,N-Dimethylglycine  Neuropeptide  Oxytocin  Plasticity  collection, management, analysis, and interpretation of the data  preparation,  review, or approval of the manuscript  or decision to submit the manuscript for  publication. There are no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. METHODS: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. RESULTS: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P(FDR) = 0.004, d = 1.13, N = 60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (P(FDR) = 0.006, r = - 0.485, N = 43) and deteriorations between 2 and 4 weeks (P(FDR) = 0.032, r = 0.415, N = 37). LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. CONCLUSION: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. TRIAL REGISTRATION: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264). En ligne : http://dx.doi.org/10.1186/s13229-021-00423-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms [texte imprimé] / Yasuhiko KATO, Auteur ; Hitoshi KUWABARA, Auteur ; Takashi OKADA, Auteur ; Toshio MUNESUE, Auteur ; Seico BENNER, Auteur ; Miho KURODA, Auteur ; Masaki KOJIMA, Auteur ; Walid YASSIN, Auteur ; Yosuke ERIGUCHI, Auteur ; Yosuke KAMENO, Auteur ; Chihiro MURAYAMA, Auteur ; Tomoko NISHIMURA, Auteur ; Kenji TSUCHIYA, Auteur ; Kiyoto KASAI, Auteur ; Norio OZAKI, Auteur ; Hirotaka KOSAKA, Auteur ; Hidenori YAMASUE, Auteur . - 15 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 15 p. Mots-clés : Administration, Intranasal  Adolescent  Adult  Autistic Disorder/blood/drug therapy/metabolism/psychology  Double-Blind Method  Facial Expression  Humans  Male  Metabolomics  Middle Aged  Oxytocin/administration & dosage/blood/pharmacokinetics  Sarcosine/analogs & derivatives/blood  Social Behavior  Treatment Outcome  Young Adult  Asperger  Autism  Clinical trial  Developmental disorders  Facial expression  N,N-Dimethylglycine  Neuropeptide  Oxytocin  Plasticity  collection, management, analysis, and interpretation of the data  preparation,  review, or approval of the manuscript  or decision to submit the manuscript for  publication. There are no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. METHODS: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. RESULTS: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P(FDR) = 0.004, d = 1.13, N = 60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (P(FDR) = 0.006, r = - 0.485, N = 43) and deteriorations between 2 and 4 weeks (P(FDR) = 0.032, r = 0.415, N = 37). LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. CONCLUSION: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. TRIAL REGISTRATION: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264). En ligne : http://dx.doi.org/10.1186/s13229-021-00423-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

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