Characteristics and Predictive Value of Blood Transcriptome Signature in Males with Autism Spectrum Disorders
Open Access
- 5 December 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (12), e49475
- https://doi.org/10.1371/journal.pone.0049475
Abstract
Autism Spectrum Disorders (ASD) is a spectrum of highly heritable neurodevelopmental disorders in which known mutations contribute to disease risk in 20% of cases. Here, we report the results of the largest blood transcriptome study to date that aims to identify differences in 170 ASD cases and 115 age/sex-matched controls and to evaluate the utility of gene expression profiling as a tool to aid in the diagnosis of ASD. The differentially expressed genes were enriched for the neurotrophin signaling, long-term potentiation/depression, and notch signaling pathways. We developed a 55-gene prediction model, using a cross-validation strategy, on a sample cohort of 66 male ASD cases and 33 age-matched male controls (P1). Subsequently, 104 ASD cases and 82 controls were recruited and used as a validation set (P2). This 55-gene expression signature achieved 68% classification accuracy with the validation cohort (area under the receiver operating characteristic curve (AUC): 0.70 [95% confidence interval [CI]: 0.62–0.77]). Not surprisingly, our prediction model that was built and trained with male samples performed well for males (AUC 0.73, 95% CI 0.65–0.82), but not for female samples (AUC 0.51, 95% CI 0.36–0.67). The 55-gene signature also performed robustly when the prediction model was trained with P2 male samples to classify P1 samples (AUC 0.69, 95% CI 0.58–0.80). Our result suggests that the use of blood expression profiling for ASD detection may be feasible. Further study is required to determine the age at which such a test should be deployed, and what genetic characteristics of ASD can be identified.Keywords
This publication has 71 references indexed in Scilit:
- Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophreniaMolecular Psychiatry, 2010
- Gene expression profiling differentiates autism case–controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autismAutism Research, 2009
- Altered gene expression and function of peripheral blood natural killer cells in children with autismBrain, Behavior, and Immunity, 2009
- Feasibility and relevance of examining lymphoblastoid cell lines to study role of microRNAs in autismAutism Research, 2008
- Immune transcriptome alterations in the temporal cortex of subjects with autismNeurobiology of Disease, 2008
- Gene expression study on peripheral blood identifies progranulin mutationsAnnals of Neurology, 2008
- Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilitiesGenomics, 2008
- Structural Variation of Chromosomes in Autism Spectrum DisorderAmerican Journal of Human Genetics, 2008
- Altered neurodevelopment associated with mutations of RSK2: a morphometric MRI study of Coffin–Lowry syndromeneurogenetics, 2007
- Gene expression profiling predicts clinical outcome of breast cancerNature, 2002