Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder / Stephen K. SIECINSKI in Autism Research, 16-3 (March 2023)  

Public ISBD [article]  inAutism Research > 16-3 (March 2023) . - p.502-523 Titre : Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Stephen K. SIECINSKI, Auteur ; Stephanie N. GIAMBERARDINO, Auteur ; Marina SPANOS, Auteur ; Annalise C. HAUSER, Auteur ; Jason R. GIBSON, Auteur ; Tara CHANDRASEKHAR, Auteur ; Maria Del Pilar TRELLES, Auteur ; Carol M. ROCKHILL, Auteur ; Michelle L. PALUMBO, Auteur ; Allyson Witters CUNDIFF, Auteur ; Alicia MONTGOMERY, Auteur ; Paige SIPER, Auteur ; Mendy MINJAREZ, Auteur ; Lisa A. NOWINSKI, Auteur ; Sarah MARLER, Auteur ; Lydia C. KWEE, Auteur ; Lauren C. SHUFFREY, Auteur ; Cheryl ALDERMAN, Auteur ; Jordana WEISSMAN, Auteur ; Brooke ZAPPONE, Auteur ; Jennifer E. MULLETT, Auteur ; Hope CROSSON, Auteur ; Natalie HONG, Auteur ; Sheng LUO, Auteur ; Lilin SHE, Auteur ; Manjushri BHAPKAR, Auteur ; Russell DEAN, Auteur ; Abby SCHEER, Auteur ; Jacqueline L. JOHNSON, Auteur ; Bryan H. KING, Auteur ; Christopher J. MCDOUGLE, Auteur ; Kevin B. SANDERS, Auteur ; Soo-Jeong KIM, Auteur ; Alexander KOLEVZON, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur ; Elizabeth R. HAUSER, Auteur ; Linmarie SIKICH, Auteur ; Simon G. GREGORY, Auteur Article en page(s) : p.502-523 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome-wide profiles of DNA-methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT. Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA-methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT-based interventions. Lay Summary Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation. We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non-DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways. These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT-based treatment. En ligne : https://doi.org/10.1002/aur.2884 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=498 [article] Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder [Texte imprimé et/ou numérique] / Stephen K. SIECINSKI, Auteur ; Stephanie N. GIAMBERARDINO, Auteur ; Marina SPANOS, Auteur ; Annalise C. HAUSER, Auteur ; Jason R. GIBSON, Auteur ; Tara CHANDRASEKHAR, Auteur ; Maria Del Pilar TRELLES, Auteur ; Carol M. ROCKHILL, Auteur ; Michelle L. PALUMBO, Auteur ; Allyson Witters CUNDIFF, Auteur ; Alicia MONTGOMERY, Auteur ; Paige SIPER, Auteur ; Mendy MINJAREZ, Auteur ; Lisa A. NOWINSKI, Auteur ; Sarah MARLER, Auteur ; Lydia C. KWEE, Auteur ; Lauren C. SHUFFREY, Auteur ; Cheryl ALDERMAN, Auteur ; Jordana WEISSMAN, Auteur ; Brooke ZAPPONE, Auteur ; Jennifer E. MULLETT, Auteur ; Hope CROSSON, Auteur ; Natalie HONG, Auteur ; Sheng LUO, Auteur ; Lilin SHE, Auteur ; Manjushri BHAPKAR, Auteur ; Russell DEAN, Auteur ; Abby SCHEER, Auteur ; Jacqueline L. JOHNSON, Auteur ; Bryan H. KING, Auteur ; Christopher J. MCDOUGLE, Auteur ; Kevin B. SANDERS, Auteur ; Soo-Jeong KIM, Auteur ; Alexander KOLEVZON, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur ; Elizabeth R. HAUSER, Auteur ; Linmarie SIKICH, Auteur ; Simon G. GREGORY, Auteur . - p.502-523. Langues : Anglais (eng) in Autism Research > 16-3 (March 2023) . - p.502-523 Index. décimale : PER Périodiques Résumé : Abstract Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome-wide profiles of DNA-methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT. Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA-methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT-based interventions. Lay Summary Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation. We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non-DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways. These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT-based treatment. En ligne : https://doi.org/10.1002/aur.2884 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=498

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