Authors
Aojie Lian, Qiong Wang, Mei He, Hong Zhang
Published in
Functional & integrative genomics. Volume 26. Issue 1. Jul 08, 2026. Epub Jul 08, 2026.
Abstract
Autism spectrum disorder (ASD) risk genes converge on synaptic and developmental regulatory biology, but it remains unclear whether fixed risk-gene sets retain the same functional meaning across prenatal and adult cortical contexts. We analyzed predefined ASD risk-gene sets across BrainSpan developmental transcriptomics, three adult cortical bulk cohorts, fetal and adult single-cell resources, composition-aware bulk models, SynGO and Reactome annotations, matched-random controls, correlation-aware gene-set tests, and STRING physical-interaction networks. The broad SFARI gene set showed the strongest adult cortex ASD-control meta-analytic reduction, driven mainly by its SynGO-annotated synaptic component. This adult signal remained significant in Gandal2022 after donor-aware modeling, donor-level aggregation, mixed-effects modeling, covariate sensitivity analyses, outlier checks, and drop-one-reference composition adjustment. Size-matched gene-level resampling indicated that the signal was not explained by gene-set size alone, whereas expression-matched controls supported a more conservative interpretation involving expression-level background properties. In contrast, the mid-prenatal top-20% SFARI subset localized more strongly to fetal progenitor-to-neurogenic states and chromatin-regulatory Reactome terms but did not show a stable adult cortical ASD-control effect. These results define an adult synaptic ASD-associated layer and a mid-prenatal developmental-regulatory layer within predefined ASD risk-gene sets.
PMID:
42418076
Bibliographic data and abstract were imported from PubMed on 08 Jul 2026.
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