Abstract
Background: Recently, HSPA1A and YBX3 have been suggested as influential genes for Autism Spectrum Disorder (ASD). However, the results have shown a lack of replication. Method: Here we performed a systematic review and a meta-analysis to explore the gene expression activity of HSPA1A and YBX3 in ASD. Fifteen RNA expression datasets of ASD case vs. control studies were acquired from Gene Expression Omnibus, including 1,534 samples (830 ASD cases, and 704 healthy controls). Both fixed-effect and random-effects models were employed for meta-analysis. Multiple linear regression (MLR) were employed to study the possible influence of the following factors: tissue, sample size, sex and racial region. Results: Utilizing all 15 datasets, both genes presented no significant log fold change (LFC) in ASD: YBX3 (LFC = 0.001; p-value = 0.49); HSPA1A (LFC = 0.115; p-value = 0.16), but weak effect sizes for the 3 brain tissue sampled datasets: YBX3 (LOR = 0.89; p-value = 0.11); HSPA1A (LOR = 0.91; p-value = 0.086). Sample tissue is a major factor for both genes (p-value < 1.5e-04) and sex is for HSPA1A only (p-value < 0.01). Literature based pathway analysis show that YBX3 and HSPA1A may play inhibitory roles again ASD. Conclusion: Our results suggest that YBX3 and HSPA1A may present weak protective regulation within the brain of ASD patients.
Highlights
IntroductionAutism Spectrum Disorder (ASD) describes a range of conditions classified as neurodevelopmental disorders with high heritability . [1,2,3] Both family and twin studies suggest that ASDs are highly heritable neuropsychiatric disorders . [4,5] the specific causes of ASD have yet to be found, it is believed that the genetic or environmental risk factors perturb common underlying molecular pathways in the brain that may contribute to the ASD pathogenesis [6].Data from brain regions and blood at the gene expression levels were well-employed in efforts to identify ASD genetic determinants . [7,8,9] Recently, two novel genes, YBX3 and HSPA1A, were proposed to play significant roles in the pathogenesis of ASD . [10] The study was conducted using gene expression and large scale literature data, with pathway enrichment analysis (PEA) and network connectivity analysis (NCA) conducted to analyze the potential functional association between these two genes and ASD
Literature based pathway analysis show that YBX3 and HSPA1A may play inhibitory roles again Autism Spectrum Disorder (ASD)
Our results suggest that YBX3 and HSPA1A may present weak protective regulation within the brain of ASD patients
Summary
Autism Spectrum Disorder (ASD) describes a range of conditions classified as neurodevelopmental disorders with high heritability . [1,2,3] Both family and twin studies suggest that ASDs are highly heritable neuropsychiatric disorders . [4,5] the specific causes of ASD have yet to be found, it is believed that the genetic or environmental risk factors perturb common underlying molecular pathways in the brain that may contribute to the ASD pathogenesis [6].Data from brain regions and blood at the gene expression levels were well-employed in efforts to identify ASD genetic determinants . [7,8,9] Recently, two novel genes, YBX3 and HSPA1A, were proposed to play significant roles in the pathogenesis of ASD . [10] The study was conducted using gene expression and large scale literature data, with pathway enrichment analysis (PEA) and network connectivity analysis (NCA) conducted to analyze the potential functional association between these two genes and ASD. [1,2,3] Both family and twin studies suggest that ASDs are highly heritable neuropsychiatric disorders . Data from brain regions and blood at the gene expression levels were well-employed in efforts to identify ASD genetic determinants . [7,8,9] Recently, two novel genes, YBX3 and HSPA1A, were proposed to play significant roles in the pathogenesis of ASD . [10] The study was conducted using gene expression and large scale literature data, with pathway enrichment analysis (PEA) and network connectivity analysis (NCA) conducted to analyze the potential functional association between these two genes and ASD. HSPA1A and YBX3 have been suggested as influential genes for Autism Spectrum Disorder (ASD).
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