A Protective Super-Enhancer Variant Regulating SLC7A7 Modulates Autism Spectrum Disorder Risk: A Cross-Population Study / Jiao ZHANG in Autism Research, 19-4 (April 2026)  

Public ISBD [article]  inAutism Research > 19-4 (April 2026) . - e70201 Titre : A Protective Super-Enhancer Variant Regulating SLC7A7 Modulates Autism Spectrum Disorder Risk: A Cross-Population Study Type de document : texte imprimé Auteurs : Jiao ZHANG, Auteur ; Fang HOU, Auteur ; Yanlin CHEN, Auteur ; Qianhui CHEN, Auteur ; Zhen XIANG, Auteur ; Tianchun WANG, Auteur ; Xi LIANG, Auteur ; Li LI, Auteur ; Ranran SONG, Auteur Article en page(s) : e70201 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  gene expression  genome-wide association study  rs1951568  single nucleotide polymorphism  super enhancers Index. décimale : PER Périodiques Résumé : ABSTRACT Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental condition with a rising global prevalence. However, the functional role of super-enhancers, the key genomic regulatory elements, remains largely uncharacterized in ASD. This study aims to identify functional single-nucleotide polymorphisms (SNPs) within super-enhancers that regulate ASD-associated genes and to validate their contribution to ASD risk. We integrated 1394 ASD susceptibility genes with 1315 differentially expressed genes and 2954 super-enhancers from the cerebral cortex. SNPs located in these regions were prioritized through expression quantitative trait locus (eQTL) analysis (p?A variant, located within the super-enhancer regulating SLC7A7, demonstrated a significant association with reduced ASD risk in the Chinese population (OR?=?0.783, 95% CI: 0.604?0.957, p?=?0.017). The protective association was further replicated in the European population (A allele vs. G allele, OR?=?0.963, 95% CI: 0.935?0.992, p?=?0.012). The eQTL analysis linked the rs1951568-A allele to reduced SLC7A7 expression. Functional characterization confirmed the variant's regulatory activity and predicted that the A allele enhanced binding motifs for the transcriptional repressors TBX5 and ZEB1. Our findings identify rs1951568-A as a novel protective variant for ASD within a SLC7A7 super-enhancer. This allele likely confers protection by modulating SLC7A7 expression, potentially through enhanced repressor binding, highlighting the importance of super-enhancer variants in ASD etiology. En ligne : https://doi.org/10.1002/aur.70201 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=585 [article] A Protective Super-Enhancer Variant Regulating SLC7A7 Modulates Autism Spectrum Disorder Risk: A Cross-Population Study [texte imprimé] / Jiao ZHANG, Auteur ; Fang HOU, Auteur ; Yanlin CHEN, Auteur ; Qianhui CHEN, Auteur ; Zhen XIANG, Auteur ; Tianchun WANG, Auteur ; Xi LIANG, Auteur ; Li LI, Auteur ; Ranran SONG, Auteur . - e70201. Langues : Anglais (eng) in Autism Research > 19-4 (April 2026) . - e70201 Mots-clés : autism spectrum disorder  gene expression  genome-wide association study  rs1951568  single nucleotide polymorphism  super enhancers Index. décimale : PER Périodiques Résumé : ABSTRACT Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental condition with a rising global prevalence. However, the functional role of super-enhancers, the key genomic regulatory elements, remains largely uncharacterized in ASD. This study aims to identify functional single-nucleotide polymorphisms (SNPs) within super-enhancers that regulate ASD-associated genes and to validate their contribution to ASD risk. We integrated 1394 ASD susceptibility genes with 1315 differentially expressed genes and 2954 super-enhancers from the cerebral cortex. SNPs located in these regions were prioritized through expression quantitative trait locus (eQTL) analysis (p?A variant, located within the super-enhancer regulating SLC7A7, demonstrated a significant association with reduced ASD risk in the Chinese population (OR?=?0.783, 95% CI: 0.604?0.957, p?=?0.017). The protective association was further replicated in the European population (A allele vs. G allele, OR?=?0.963, 95% CI: 0.935?0.992, p?=?0.012). The eQTL analysis linked the rs1951568-A allele to reduced SLC7A7 expression. Functional characterization confirmed the variant's regulatory activity and predicted that the A allele enhanced binding motifs for the transcriptional repressors TBX5 and ZEB1. Our findings identify rs1951568-A as a novel protective variant for ASD within a SLC7A7 super-enhancer. This allele likely confers protection by modulating SLC7A7 expression, potentially through enhanced repressor binding, highlighting the importance of super-enhancer variants in ASD etiology. En ligne : https://doi.org/10.1002/aur.70201 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=585

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