Candidate Peripheral Blood Transcriptomic Signals Associated with Autism Spectrum Disorder: Re-analysis of Public Dataset GSE111175

Abstract

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition for which diagnosis remains primarily behavioural, while robust blood-based molecular markers remain investigational. This study re-analysed publicly available peripheral blood leukocyte microarray data from the Gene Expression Omnibus series GSE111175 to characterise transcriptomic differences between male toddlers with ASD and Typically Developing (TD) controls. The two-group analysis comprised 98 samples (28 ASD and 70 TD) measured on the Illumina HumanHT-12 V4.0 platform. Differential expression was evaluated with GEO2R/limma using Benjamini-Hochberg false-discovery-rate correction, with statistical significance defined as an adjusted P value < 0.05 and no additional absolute log2-fold-change threshold. The re-analysis identified 129 significant transcript probes, including 77 with positive and 52 with negative log2 fold changes in ASD relative to TD. Among the prioritised probes, TOMM5 and NDUFA12 showed modest negative log2 fold changes, whereas PHF2, IP6K1, GABARAPL1 and ABCA1 showed modest positive changes. These observations are biologically compatible with mitochondrial, autophagy-related and lipid-homeostasis processes, but the present probe-level associations do not establish pathway dysfunction, causal mechanisms or clinical diagnostic performance. Accordingly, the findings should be regarded as discovery-stage peripheral transcriptomic signals that require replication in independent cohorts, adjustment for leukocyte composition and other covariates, and prospective validation before biomarker utility can be inferred.