![]() ![]() 9, 13, 16, 17, 18, 19, 20, 21 However, none of these have provided adequate specificity or accuracy to be used in ASD diagnosis. 3, 4, 5 The search for genetic loci in ASD, including linkage and genome-wide association screens (GWAS), has identified a number of candidate genes and loci on almost every chromosome, 6, 7, 8, 9, 10, 11 with multiple hotspots on several chromosomes (for example, CNTNAP2, NGLNX4, NRXN1, IMMP2L, DOCK4, SEMA5A, SYNGAP1, DLGAP2, SHANK2 and SHANK3), 7, 12, 13, 14, 15 and copy number variations. 2 The etiology of ASD is poorly understood, however, a genetic basis is evidenced by the greater than 70% concordance in monozygotic twins and elevated risk in siblings compared with the population. Similar content being viewed by othersĪutism spectrum disorders (ASDs) are a complex group of sporadic and familial developmental disorders affecting 1 in 150 births 1 and characterized by: abnormal social interaction, impaired communication and stereotypic behaviors. Our results have wide implications for detection, intervention and prevention of ASD. While SNPs differ across ethnic groups, our pathway approach identified cellular processes common to ASD across ethnicities. In conclusion, we have developed an accurate diagnostic test for a genetically homogeneous group to aid in early detection of ASD. 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. Prediction accuracy diminished as the number of SNPs analyzed in the model was decreased. 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. 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). 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 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. SNPs were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived pathways to identify affected cellular processes and develop a diagnostic test. The current investigation interrogated single-nucleotide polymorphisms (SNPs) of individuals with ASD from the Autism Genetic Resource Exchange (AGRE) database. Autism spectrum disorder (ASD) depends on a clinical interview with no biomarkers to aid diagnosis. ![]()
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