Predicting the diagnosis of autism spectrum disorder using gene pathway analysis

Autor: Renee Testa, Christos Pantelis, Efstratios Skafidas, Ian P. Everall, Daniela Zantomio, Gursharan Chana
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
autistic disorder/diagnosis
predictive testing
Large-Conductance Calcium-Activated Potassium Channel beta Subunits
childhood development disorders
Receptor
Metabotropic Glutamate 5
Single-nucleotide polymorphism
Nerve Tissue Proteins
GTP-Binding Protein alpha Subunits
Gi-Go
Polymorphism
Single Nucleotide
White People
Cohort Studies
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Asian People
mental disorders
Medicine
Humans
Gene Regulatory Networks
Genetic Predisposition to Disease
Copy-number variation
Genetic Testing
Predictive testing
Molecular Biology
030304 developmental biology
Genetic testing
Genetics
0303 health sciences
medicine.diagnostic_test
business.industry
medicine.disease
3. Good health
Psychiatry and Mental health
classification
Autism spectrum disorder
Child Development Disorders
Pervasive
Cohort
Autism
Female
Original Article
business
030217 neurology & neurosurgery
Cohort study
Zdroj: Molecular Psychiatry
ISSN: 1476-5578
1359-4184
Popis: 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.
Databáze: OpenAIRE
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