Protein-Altering Variants' Analysis in Autism Subgroups Uncovers Early Brain-Expressed Gene Modules Relevant to Autism Pathophysiology / Gaia SCACCABAROZZI in Autism Research, 18-8 (August 2025)  

Public ISBD [article]  inAutism Research > 18-8 (August 2025) . - p.1535-1549 Titre : Protein-Altering Variants' Analysis in Autism Subgroups Uncovers Early Brain-Expressed Gene Modules Relevant to Autism Pathophysiology Type de document : Texte imprimé et/ou numérique Auteurs : Gaia SCACCABAROZZI, Auteur ; Luca FUMAGALLI, Auteur ; Maddalena MAMBRETTI, Auteur ; Roberto GIORDA, Auteur ; Marco VILLA, Auteur ; Silvia BUSTI CECCARELLI, Auteur ; Laura VILLA, Auteur ; Elisa MANI, Auteur ; Maria NOBILE, Auteur ; Massimo MOLTENI, Auteur ; Uberto POZZOLI, Auteur ; Alessandro CRIPPA, Auteur Article en page(s) : p.1535-1549 Langues : Anglais (eng) Mots-clés : autism  brain expression  genetics  heterogeneity  protein-altering variants Index. décimale : PER Périodiques Résumé : ABSTRACT Understanding the functional implications of genes' variants in autism heterogeneity is challenging. Gene set analysis examines the cumulative effect of multiple functionally converging genes. Here we explored whether a multi-step analysis could identify gene sets with different loads of protein-altering variants (PAVs) between two subgroups of autistic children. After subdividing our sample (n?=?71, 3?12?years) based on higher (>?80; n?=?43) and lower (? 80; n?=?28) intelligence quotient (IQ), a gene set variant enrichment analysis identified gene sets with significantly different incidence of PAVs between the two subgroups of autistic children. Significant gene sets were then clustered into modules of genes. Their brain expression was investigated according to the BrainSpan Atlas of the Developing Human Brain. Next, we extended each module by selecting the genes that were spatio-temporally co-expressed in the developing brain and physically interacting with those in modules. Last, we explored the incidence of autism susceptibility genes within original and extended modules. Our analysis identified 38 significant gene sets (FDR, q? En ligne : https://doi.org/10.1002/aur.70086 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=566 [article] Protein-Altering Variants' Analysis in Autism Subgroups Uncovers Early Brain-Expressed Gene Modules Relevant to Autism Pathophysiology [Texte imprimé et/ou numérique] / Gaia SCACCABAROZZI, Auteur ; Luca FUMAGALLI, Auteur ; Maddalena MAMBRETTI, Auteur ; Roberto GIORDA, Auteur ; Marco VILLA, Auteur ; Silvia BUSTI CECCARELLI, Auteur ; Laura VILLA, Auteur ; Elisa MANI, Auteur ; Maria NOBILE, Auteur ; Massimo MOLTENI, Auteur ; Uberto POZZOLI, Auteur ; Alessandro CRIPPA, Auteur . - p.1535-1549. Langues : Anglais (eng) in Autism Research > 18-8 (August 2025) . - p.1535-1549 Mots-clés : autism  brain expression  genetics  heterogeneity  protein-altering variants Index. décimale : PER Périodiques Résumé : ABSTRACT Understanding the functional implications of genes' variants in autism heterogeneity is challenging. Gene set analysis examines the cumulative effect of multiple functionally converging genes. Here we explored whether a multi-step analysis could identify gene sets with different loads of protein-altering variants (PAVs) between two subgroups of autistic children. After subdividing our sample (n?=?71, 3?12?years) based on higher (>?80; n?=?43) and lower (? 80; n?=?28) intelligence quotient (IQ), a gene set variant enrichment analysis identified gene sets with significantly different incidence of PAVs between the two subgroups of autistic children. Significant gene sets were then clustered into modules of genes. Their brain expression was investigated according to the BrainSpan Atlas of the Developing Human Brain. Next, we extended each module by selecting the genes that were spatio-temporally co-expressed in the developing brain and physically interacting with those in modules. Last, we explored the incidence of autism susceptibility genes within original and extended modules. Our analysis identified 38 significant gene sets (FDR, q? En ligne : https://doi.org/10.1002/aur.70086 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=566

---

1 (1 - 1 / 1)