Original Article

Molecular Psychiatry (2014) 19, 504–510; doi:10.1038/mp.2012.126; published online 11 September 2012

Predicting the diagnosis of autism spectrum disorder using gene pathway analysis

E Skafidas1, R Testa2,3, D Zantomio4, G Chana5, I P Everall5 and C Pantelis2,5

  1. 1Centre for Neural Engineering, The University of Melbourne, Parkville, VIC, Australia
  2. 2Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Parkville, VIC, Australia
  3. 3Department of Psychology, Monash University, Clayton, VIC, Australia
  4. 4Department of Haematology, Austin Health, Heidelberg, VIC, Australia
  5. 5Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia

Correspondence: Professor C Pantelis, National Neuroscience Facility (NNF), Level 3, 161 Barry Street, Carlton South, VIC 3053, Australia. E-mail: cpant@unimelb.edu.au

Received 6 July 2012; Accepted 9 July 2012
Advance online publication 11 September 2012



Autism spectrum disorder (ASD) depends on a clinical interview with no biomarkers to aid diagnosis. The current investigation interrogated single-nucleotide polymorphisms (SNPs) of individuals with ASD from the Autism Genetic Resource Exchange (AGRE) database. SNPs were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived pathways to identify affected cellular processes and develop a diagnostic test. This test was then applied to two independent samples from the Simons Foundation Autism Research Initiative (SFARI) and Wellcome Trust 1958 normal birth cohort (WTBC) for validation. Using AGRE SNP data from a Central European (CEU) cohort, we created a genetic diagnostic classifier consisting of 237 SNPs in 146 genes that correctly predicted ASD diagnosis in 85.6% of CEU cases. This classifier also predicted 84.3% of cases in an ethnically related Tuscan cohort; however, prediction was less accurate (56.4%) in a genetically dissimilar Han Chinese cohort (HAN). Eight SNPs in three genes (KCNMB4, GNAO1, GRM5) had the largest effect in the classifier with some acting as vulnerability SNPs, whereas others were protective. Prediction accuracy diminished as the number of SNPs analyzed in the model was decreased. Our diagnostic classifier correctly predicted ASD diagnosis with an accuracy of 71.7% in CEU individuals from the SFARI (ASD) and WTBC (controls) validation data sets. In conclusion, we have developed an accurate diagnostic test for a genetically homogeneous group to aid in early detection of ASD. While SNPs differ across ethnic groups, our pathway approach identified cellular processes common to ASD across ethnicities. Our results have wide implications for detection, intervention and prevention of ASD.


autistic disorder/diagnosis; classification; childhood development disorders; predictive testing