Characteristics and Predictive Value of Blood Transcriptome Signature in Males with Autism Spectrum Disorders

Sek Won Kong, Christin D. Collins, Yuko Shimizu-Motohashi, Ingrid A. Holm, Malcolm G. Campbell, In Hee Lee, Stephanie J. Brewster, Ellen Hanson, Heather K. Harris, Kathryn R. Lowe, Adrianna Saada, Andrea Mora, Kimberly Madison, Rachel Hundley, Jessica Egan, Jillian McCarthy, Ally Eran, Michal Galdzicki, Leonard Rappaport, Louis M. KunkelIsaac S. Kohane

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


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.

Original languageEnglish
Article numbere49475
JournalPLoS ONE
Issue number12
StatePublished - 5 Dec 2012
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Characteristics and Predictive Value of Blood Transcriptome Signature in Males with Autism Spectrum Disorders'. Together they form a unique fingerprint.

Cite this